Top

Published in:

01-09-2014

Androgen receptor signaling in prostate cancer

Authors: Zoran Culig, Frédéric R. Santer

Published in: Cancer and Metastasis Reviews | Issue 2-3/2014

Abstract

The androgen receptor (AR), ligand-induced transcription factor, is expressed in primary prostate cancer and in metastases. AR regulates multiple cellular events, proliferation, apoptosis, migration, invasion, and differentiation. Its expression in prostate cancer cells is regulated by steroid and peptide hormones. AR downregulation by various compounds which are contained in fruits and vegetables is considered a chemopreventive strategy for prostate cancer. There is a bidirectional interaction between the AR and micro-RNA (miRNA) in prostate cancer; androgens may upregulate or downregulate the selected miRNA, whereas the AR itself is a target of miRNA. AR mutations have been discovered in prostate cancer, and their incidence may increase with tumor progression. AR mutations and increased expression of selected coactivators contribute to the acquisition of agonistic properties of anti-androgens. Expression of some of the coactivators is enhanced during androgen ablation. AR activity is regulated by peptides such as cytokines or growth factors which reduce the concentration of androgen required for maximal stimulation of the receptor. In prostate cancer, variant ARs which exhibit constitutive activity were detected. Novel therapies which interfere with intracrine synthesis of androgens or inhibit nuclear translocation of the AR have been introduced in the clinic.

van der Kwast, T. H., Schalken, J., Ruizeveld de Winter, J. A., van Vroonhoven, C. C., Mulder, E., Boersma, W., et al. (1991). Androgen receptors in endocrine-therapy-resistant human prostate cancer. International Journal of Cancer, 48, 189–193.

Hobisch, A., Culig, Z., Radmayr, C., Bartsch, G., Klocker, H., & Hittmair, A. (1995). Distant metastases from prostatic carcinoma express androgen receptor protein. Cancer Research, 55, 3068–3072.PubMed

Lu, S., Tsai, S. Y., & Tsai, M. J. (1997). Regulation of androgen-dependent prostatic cancer cell growth: androgen regulation of CDK2, CDK4, and CKI p16 genes. Cancer Research, 57, 4511–4516.PubMed

Attardi, B. J., Burgenson, J., Hild, S. A., & Reel, J. R. (2004). Steroid hormonal regulation of growth, prostate specific antigen secretion, and transcription mediated by the mutated androgen receptor in CWR22Rv1 human prostate carcinoma cells. Molecular and Cellular Endocrinology, 222, 121–132.PubMed

Zhao, X. Y., Boyle, B., Krishnan, A. V., Navone, N. M., Peehl, D. M., & Feldman, D. (1999). Two mutations identified in the androgen receptor of the new human prostate cancer cell line MDA PCa 2a. The Journal of Urology, 162, 2192–2199.PubMed

Denmeade, S. R., Sokoll, L. J., Dalrymple, S., Rosen, D. M., Gady, A. M., Bruzek, D., et al. (2003). Dissociation between androgen responsiveness for malignant growth vs. expression of prostate specific differentiation markers PSA, hK2, and PSMA in human prostate cancer models. The Prostate, 54, 249–257.PubMed

Heisler, L. E., Evangelou, A., Lew, A. M., Trachtenberg, J., Elsholtz, H. P., & Brown, T. J. (1997). Androgen-dependent cell cycle arrest and apoptotic death in PC-3 prostatic cell cultures expressing a full-length human androgen receptor. Molecular and Cellular Endocrinology, 126, 59–73.PubMed

Hsieh, T. C., & Wu, J. M. (1999). Differential effects on growth, cell cycle arrest, and induction of apoptosis by resveratrol in human prostate cancer cell lines. Experimental Cell Research, 249, 109–115.PubMed

Kyprianou, N., & Isaacs, J. T. (1989). Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. Molecular Endocrinology, 3, 1515–1522.PubMed

10.

Brodin, G., ten Dijke, P., Funa, K., Heldin, C. H., & Landström, M. (1999). Increased smad expression and activation are associated with apoptosis in normal and malignant prostate after castration. Cancer Research, 59, 2731–2738.PubMed

11.

Hayes, S. A., Zarnegar, M., Sharma, M., Yang, F., Peehl, D. M., ten Dijke, P., et al. (2001). SMAD3 represses androgen receptor-mediated transcription. Cancer Research, 61, 2112–2118.PubMed

12.

Kyprianou, N., & Isaacs, J. T. (1988). Identification of a cellular receptor for transforming growth factor-beta in rat ventral prostate and its negative regulation by androgens. Endocrinology, 123, 2124–2131.PubMed

13.

Eder, I. E., Culig, Z., Ramoner, R., Thurnher, M., Putz, T., Nessler-Menardi, C., et al. (2000). Inhibition of LncaP prostate cancer cells by means of androgen receptor antisense oligonucleotides. Cancer Gene Therapy, 7, 997–1007.PubMed

14.

Wang, L. G., Ossowski, L., & Ferrari, A. C. (2001). Overexpressed androgen receptor linked to p21WAF1 silencing may be responsible for androgen independence and resistance to apoptosis of a prostate cancer cell line. Cancer Research, 61, 7544–7551.PubMed

15.

Lin, Y., Lu, Z., Kokontis, J., & Xiang, J. (2013). Androgen receptor primes prostate cancer cells to apoptosis through down-regulation of basal p21 expression. Biochemical and Biophysical Research Communications, 430, 289–293.PubMed

16.

Rokhlin, O. W., Glover, R. B., Guseva, N. V., Taghiyev, A. F., Kohlgraf, K. G., & Cohen, M. B. (2006). Mechanisms of cell death induced by histone deacetylase inhibitors in androgen receptor-positive prostate cancer cells. Molecular Cancer Research: MCR, 4, 113–123.PubMed

17.

Zoubeidi, A., Zardan, A., Beraldi, E., Fazli, L., Sowery, R., Rennie, P., et al. (2007). Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Research, 67, 10455–10465.PubMed

18.

Cornforth, A. N., Davis, J. S., Khanifar, E., Nastiuk, K. L., & Krolewski, J. J. (2008). FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells. Oncogene, 27, 4422–4433.PubMed

19.

Lin, H.-K., Hu, Y.-C., Yang, L., Altuwaijri, S., Chen, Y.-T., Kang, H.-Y., et al. (2003). Suppression versus induction of androgen receptor functions by the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer LNCaP cells with different passage numbers. The Journal of Biological Chemistry, 278, 50902–50907.PubMed

20.

Wang, Y., Mikhailova, M., Bose, S., Pan, C.-X., deVere White, R. W., & Ghosh, P. M. (2008). Regulation of androgen receptor transcriptional activity by rapamycin in prostate cancer cell proliferation and survival. Oncogene, 27, 7106–7117.PubMedCentralPubMed

21.

Ha, S., Ruoff, R., Kahoud, N., Franke, T. F., & Logan, S. K. (2011). Androgen receptor levels are upregulated by Akt in prostate cancer. Endocrine-Related Cancer, 18, 245–255.PubMedCentralPubMed

22.

Liao, X., Thrasher, J. B., Pelling, J., Holzbeierlein, J., Sang, Q.-X. A., & Li, B. (2003). Androgen stimulates matrix metalloproteinase-2 expression in human prostate cancer. Endocrinology, 144, 1656–1663.PubMed

23.

Chuan, Y.-C., Pang, S.-T., Cedazo-Minguez, A., Norstedt, G., Pousette, A., & Flores-Morales, A. (2006). Androgen induction of prostate cancer cell invasion is mediated by ezrin. The Journal of Biological Chemistry, 281, 29938–29948.PubMed

24.

Hara, T., Miyazaki, H., Lee, A., Tran, C. P., & Reiter, R. E. (2008). Androgen receptor and invasion in prostate cancer. Cancer Research, 68, 1128–1135.PubMed

25.

Gohji, K., Fujimoto, N., Hara, I., Fujii, A., Gotoh, A., Okada, H., et al. (1998). Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension. International Journal of Cancer, 79, 96–101.

26.

Castoria, G., D’Amato, L., Ciociola, A., Giovannelli, P., Giraldi, T., Sepe, L., et al. (2011). Androgen-induced cell migration: role of androgen receptor/filamin A association. PloS One, 6, e17218.PubMedCentralPubMed

27.

Gerhardt, J., Montani, M., Wild, P., Beer, M., Huber, F., Hermanns, T., et al. (2012). FOXA1 promotes tumor progression in prostate cancer and represents a novel hallmark of castration-resistant prostate cancer. The American Journal of Pathology, 180, 848–861.PubMed

28.

Bonaccorsi, L., Carloni, V., Muratori, M., Salvadori, A., Giannini, A., Carini, M., et al. (2000). Androgen receptor expression in prostate carcinoma cells suppresses alpha6beta4 integrin-mediated invasive phenotype. Endocrinology, 141, 3172–3182.PubMed

29.

Zhu, M.-L., Horbinski, C. M., Garzotto, M., Qian, D. Z., Beer, T. M., & Kyprianou, N. (2010). Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer. Cancer Research, 70, 7992–8002.PubMedCentralPubMed

30.

Sun, Y., Wang, B.-E., Leong, K. G., Yue, P., Li, L., Jhunjhunwala, S., et al. (2012). Androgen deprivation causes epithelial-mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Research, 72, 527–536.PubMed

31.

Krongrad, A., Wilson, C. M., Wilson, J. D., Allman, D. R., & McPhaul, M. J. (1991). Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells. Molecular and Cellular Endocrinology, 76, 79–88.PubMed

32.

Kokontis, J., Takakura, K., Hay, N., & Liao, S. (1994). Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation. Cancer Research, 54, 1566–1573.PubMed

33.

Culig, Z., Hoffmann, J., Erdel, M., Eder, I. E., Hobisch, A., Hittmair, A., et al. (1999). Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system. British Journal of Cancer, 81, 242–251.PubMedCentralPubMed

34.

Zegarra-Moro, O. L., Schmidt, L. J., Huang, H., & Tindall, D. J. (2002). Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Research, 62, 1008–1013.PubMed

35.

Visakorpi, T., Hyytinen, E., Koivisto, P., Tanner, M., Keinänen, R., Palmberg, C., et al. (1995). In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nature Genetics, 9, 401–406.PubMed

36.

Mitchell, S. H., Zhu, W., & Young, C. Y. (1999). Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Research, 59, 5892–5895.PubMed

37.

Zhu, W., Zhang, J. S., & Young, C. Y. (2001). Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP. Carcinogenesis, 22, 1399–1403.PubMed

38.

Neuwirt, H., Arias, M. C., Puhr, M., Hobisch, A., & Culig, Z. (2008). Oligomeric proanthocyanidin complexes (OPC) exert anti-proliferative and pro-apoptotic effects on prostate cancer cells. The Prostate, 68, 1647–1654.PubMed

39.

Zhao, X. Y., Ly, L. H., Peehl, D. M., & Feldman, D. (1997). 1alpha,25-dihydroxyvitamin D3 actions in LNCaP human prostate cancer cells are androgen-dependent. Endocrinology, 138, 3290–3298.PubMed

40.

Sadar, M. D., & Gleave, M. E. (2000). Ligand-independent activation of the androgen receptor by the differentiation agent butyrate in human prostate cancer cells. Cancer Research, 60, 5825–5831.PubMed

41.

Fang, Y.-X., & Gao, W.-Q. (2013). Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene. doi:10.1038/onc.2013.54.

42.

Waltering, K. K., Porkka, K. P., Jalava, S. E., Urbanucci, A., Kohonen, P. J., Latonen, L. M., et al. (2011). Androgen regulation of micro-RNAs in prostate cancer. The Prostate, 71, 604–614.PubMed

43.

Boll, K., Reiche, K., Kasack, K., Mörbt, N., Kretzschmar, A. K., Tomm, J. M., et al. (2013). miR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene, 32, 277–285.PubMed

44.

Sun, T., Wang, Q., Balk, S., Brown, M., Lee, G.-S. M., & Kantoff, P. (2009). The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Research, 69, 3356–3363.PubMedCentralPubMed

45.

Spahn, M., Kneitz, S., Scholz, C.-J., Stenger, N., Rüdiger, T., Ströbel, P., et al. (2010). Expression of microRNA-221 is progressively reduced in aggressive prostate cancer and metastasis and predicts clinical recurrence. International Journal of Cancer, 127, 394–403.

46.

Ribas, J., Ni, X., Haffner, M., Wentzel, E. A., Salmasi, A. H., Chowdhury, W. H., et al. (2009). miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Research, 69, 7165–7169.PubMedCentralPubMed

47.

Cao, P., Deng, Z., Wan, M., Huang, W., Cramer, S. D., Xu, J., et al. (2010). MicroRNA-101 negatively regulates Ezh2 and its expression is modulated by androgen receptor and HIF-1alpha/HIF-1beta. Molecular Cancer, 9, 108.PubMedCentralPubMed

48.

Östling, P., Leivonen, S.-K., Aakula, A., Kohonen, P., Mäkelä, R., Hagman, Z., et al. (2011). Systematic analysis of microRNAs targeting the androgen receptor in prostate cancer cells. Cancer Research, 71, 1956–1967.PubMed

49.

Rokhlin, O. W., Scheinker, V. S., Taghiyev, A. F., Bumcrot, D., Glover, R. A., & Cohen, M. B. (2008). MicroRNA-34 mediates AR-dependent p53-induced apoptosis in prostate cancer. Cancer Biology & Therapy, 7, 1288–1296.

50.

Kashat, M., Azzouz, L., Sarkar, S. H., Kong, D., Li, Y., & Sarkar, F. H. (2012). Inactivation of AR and Notch-1 signaling by miR-34a attenuates prostate cancer aggressiveness. American Journal of Translational Research, 4, 432–442.PubMedCentralPubMed

51.

Sikand, K., Slaibi, J. E., Singh, R., Slane, S. D., & Shukla, G. C. (2011). miR 488* inhibits androgen receptor expression in prostate carcinoma cells. International Journal of Cancer, 129, 810–819.

52.

Lin, P.-C., Chiu, Y.-L., Banerjee, S., Park, K., Mosquera, J. M., Giannopoulou, E., et al. (2013). Epigenetic repression of miR-31 disrupts androgen receptor homeostasis and contributes to prostate cancer progression. Cancer Research, 73, 1232–1244.PubMedCentralPubMed

53.

Nadiminty, N., Tummala, R., Lou, W., Zhu, Y., Zhang, J., Chen, X., et al. (2012). MicroRNA let-7c suppresses androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells. The Journal of Biological Chemistry, 287, 1527–1537.PubMedCentralPubMed

54.

Massard, C., & Fizazi, K. (2011). Targeting continued androgen receptor signaling in prostate cancer. Clinical Cancer Research, 17, 3876–3883.PubMed

55.

Veldscholte, J., Berrevoets, C. A., Brinkmann, A. O., Grootegoed, J. A., & Mulder, E. (1992). Anti-androgens and the mutated androgen receptor of LNCaP cells: differential effects on binding affinity, heat-shock protein interaction, and transcription activation. Biochemistry, 31, 2393–2399.PubMed

56.

Sun, C., Shi, Y., Xu, L. L., Nageswararao, C., Davis, L. D., Segawa, T., et al. (2006). Androgen receptor mutation (T877A) promotes prostate cancer cell growth and cell survival. Oncogene, 25, 3905–3913.PubMed

57.

Tepper, C. G., Boucher, D. L., Ryan, P. E., Ma, A.-H., Xia, L., Lee, L.-F., et al. (2002). Characterization of a novel androgen receptor mutation in a relapsed CWR22 prostate cancer xenograft and cell line. Cancer Research, 62, 6606–6614.PubMed

58.

Culig, Z., Hobisch, A., Cronauer, M. V., Cato, A. C., Hittmair, A., Radmayr, C., et al. (1993). Mutant androgen receptor detected in an advanced-stage prostatic carcinoma is activated by adrenal androgens and progesterone. Molecular Endocrinology, 7, 1541–1550.PubMed

59.

Tilley, W. D., Buchanan, G., Hickey, T. E., & Bentel, J. M. (1996). Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clinical Cancer Research, 2, 277–285.PubMed

60.

Marcelli, M., Ittmann, M., Mariani, S., Sutherland, R., Nigam, R., Murthy, L., et al. (2000). Androgen receptor mutations in prostate cancer. Cancer Research, 60, 944–949.PubMed

61.

Taplin, M. E., Bubley, G. J., Shuster, T. D., Frantz, M. E., Spooner, A. E., Ogata, G. K., et al. (1995). Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. The New England Journal of Medicine, 332, 1393–1398.PubMed

62.

Taplin, M. E., Bubley, G. J., Ko, Y. J., Small, E. J., Upton, M., Rajeshkumar, B., et al. (1999). Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist. Cancer Research, 59, 2511–2515.PubMed

63.

Haapala, K., Hyytinen, E. R., Roiha, M., Laurila, M., Rantala, I., Helin, H. J., et al. (2001). Androgen receptor alterations in prostate cancer relapsed during a combined androgen blockade by orchiectomy and bicalutamide. Laboratory Investigation, 81, 1647–1651.PubMed

64.

Hara, T., Miyazaki, J., Araki, H., Yamaoka, M., Kanzaki, N., Kusaka, M., et al. (2003). Novel mutations of androgen receptor: a possible mechanism of bicalutamide withdrawal syndrome. Cancer Research, 63, 149–153.PubMed

65.

Yoshida, T., Kinoshita, H., Segawa, T., Nakamura, E., Inoue, T., Shimizu, Y., et al. (2005). Antiandrogen bicalutamide promotes tumor growth in a novel androgen-dependent prostate cancer xenograft model derived from a bicalutamide-treated patient. Cancer Research, 65, 9611–9616.PubMed

66.

Hyytinen, E.-R., Haapala, K., Thompson, J., Lappalainen, I., Roiha, M., Rantala, I., et al. (2002). Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer. Laboratory Investigation, 82, 1591–1598.PubMed

67.

Peng, Y., Li, C. X., Chen, F., Wang, Z., Ligr, M., Melamed, J., et al. (2008). Stimulation of prostate cancer cellular proliferation and invasion by the androgen receptor co-activator ARA70. The American Journal of Pathology, 172, 225–235.PubMedCentralPubMed

68.

Miyamoto, H., Yeh, S., Wilding, G., & Chang, C. (1998). Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells. Proceedings of the National Academy of Sciences of the United States of America, 95, 7379–7384.PubMedCentralPubMed

69.

Miyamoto, H., Yeh, S., Lardy, H., Messing, E., & Chang, C. (1998). Delta5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 95, 11083–11088.PubMedCentralPubMed

70.

Heemers, H. V., Sebo, T. J., Debes, J. D., Regan, K. M., Raclaw, K. A., Murphy, L. M., et al. (2007). Androgen deprivation increases p300 expression in prostate cancer cells. Cancer Research, 67, 3422–3430.PubMed

71.

Comuzzi, B., Nemes, C., Schmidt, S., Jasarevic, Z., Lodde, M., Pycha, A., et al. (2004). The androgen receptor co-activator CBP is up-regulated following androgen withdrawal and is highly expressed in advanced prostate cancer. The Journal of Pathology, 204, 159–166.PubMed

72.

Debes, J. D., Comuzzi, B., Schmidt, L. J., Dehm, S. M., Culig, Z., & Tindall, D. J. (2005). p300 regulates androgen receptor-independent expression of prostate-specific antigen in prostate cancer cells treated chronically with interleukin-6. Cancer Research, 65, 5965–5973.PubMed

73.

Comuzzi, B., Lambrinidis, L., Rogatsch, H., Godoy-Tundidor, S., Knezevic, N., Krhen, I., et al. (2003). The transcriptional co-activator cAMP response element-binding protein-binding protein is expressed in prostate cancer and enhances androgen- and anti-androgen-induced androgen receptor function. The American Journal of Pathology, 162, 233–241.PubMedCentralPubMed

74.

Nishimura, K., Ting, H.-J., Harada, Y., Tokizane, T., Nonomura, N., Kang, H.-Y., et al. (2003). Modulation of androgen receptor transactivation by gelsolin: a newly identified androgen receptor coregulator. Cancer Research, 63, 4888–4894.PubMed

75.

Wang, Y., Kreisberg, J. I., Bedolla, R. G., Mikhailova, M., deVere White, R. W., & Ghosh, P. M. (2007). A 90 kDa fragment of filamin A promotes Casodex-induced growth inhibition in Casodex-resistant androgen receptor positive C4-2 prostate cancer cells. Oncogene, 26, 6061–6070.PubMed

76.

Santer, F. R., Höschele, P. P. S., Oh, S. J., Erb, H. H. H., Bouchal, J., Cavarretta, I. T., et al. (2011). Inhibition of the acetyltransferases p300 and CBP reveals a targetable function for p300 in the survival and invasion pathways of prostate cancer cell lines. Molecular Cancer Therapeutics, 10, 1644–1655.PubMed

77.

Halkidou, K., Gnanapragasam, V. J., Mehta, P. B., Logan, I. R., Brady, M. E., Cook, S., et al. (2003). Expression of Tip60, an androgen receptor coactivator, and its role in prostate cancer development. Oncogene, 22, 2466–2477.PubMed

78.

Shiota, M., Yokomizo, A., Masubuchi, D., Tada, Y., Inokuchi, J., Eto, M., et al. (2010). Tip60 promotes prostate cancer cell proliferation by translocation of androgen receptor into the nucleus. The Prostate, 70, 540–554.PubMed

79.

Coffey, K., Blackburn, T. J., Cook, S., Golding, B. T., Griffin, R. J., Hardcastle, I. R., et al. (2012). Characterisation of a Tip60 specific inhibitor, NU9056, in prostate cancer. PloS One, 7, e45539.PubMedCentralPubMed

80.

Agoulnik, I. U., Vaid, A., Nakka, M., Alvarado, M., Bingman, W. E., 3rd, Erdem, H., et al. (2006). Androgens modulate expression of transcription intermediary factor 2, an androgen receptor coactivator whose expression level correlates with early biochemical recurrence in prostate cancer. Cancer Research, 66, 10594–10602.PubMed

81.

Gregory, C. W., Fei, X., Ponguta, L. A., He, B., Bill, H. M., French, F. S., et al. (2004). Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer. The Journal of Biological Chemistry, 279, 7119–7130.PubMed

82.

Feng, S., Tang, Q., Sun, M., Chun, J. Y., Evans, C. P., & Gao, A. C. (2009). Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2. Molecular Cancer Therapeutics, 8, 665–671.PubMedCentralPubMed

83.

Froesch, B. A., Takayama, S., & Reed, J. C. (1998). BAG-1 L protein enhances androgen receptor function. The Journal of Biological Chemistry, 273, 11660–11666.PubMed

84.

Agoulnik, I. U., Vaid, A., Bingman, W. E., 3rd, Erdeme, H., Frolov, A., Smith, C. L., et al. (2005). Role of SRC-1 in the promotion of prostate cancer cell growth and tumor progression. Cancer Research, 65, 7959–7967.PubMed

85.

Ueda, T., Mawji, N. R., Bruchovsky, N., & Sadar, M. D. (2002). Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells. The Journal of Biological Chemistry, 277, 38087–38094.PubMed

86.

Gnanapragasam, V. J., Leung, H. Y., Pulimood, A. S., Neal, D. E., & Robson, C. N. (2001). Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer. British Journal of Cancer, 85, 1928–1936.PubMedCentralPubMed

87.

Yan, J., Yu, C.-T., Ozen, M., Ittmann, M., Tsai, S. Y., & Tsai, M.-J. (2006). Steroid receptor coactivator-3 and activator protein-1 coordinately regulate the transcription of components of the insulin-like growth factor/AKT signaling pathway. Cancer Research, 66, 11039–11046.PubMed

88.

Tien, J. C.-Y., Liu, Z., Liao, L., Wang, F., Xu, Y., Wu, Y.-L., et al. (2013). The Steroid Receptor Coactivator-3 Is Required for the Development of Castration-resistant Prostate Cancer. Cancer Research.

89.

Kaulfuss, S., Grzmil, M., Hemmerlein, B., Thelen, P., Schweyer, S., Neesen, J., et al. (2008). Leupaxin, a novel coactivator of the androgen receptor, is expressed in prostate cancer and plays a role in adhesion and invasion of prostate carcinoma cells. Molecular Endocrinology, 22, 1606–1621.PubMed

90.

Dong, Z., Liu, Y., Lu, S., Wang, A., Lee, K., Wang, L.-H., et al. (2006). Vav3 oncogene is overexpressed and regulates cell growth and androgen receptor activity in human prostate cancer. Molecular Endocrinology, 20, 2315–2325.PubMed

91.

Liu, Y., Mo, J. Q., Hu, Q., Boivin, G., Levin, L., Lu, S., et al. (2008). Targeted overexpression of vav3 oncogene in prostatic epithelium induces nonbacterial prostatitis and prostate cancer. Cancer Research, 68, 6396–6406.PubMedCentralPubMed

92.

Clark, E. L., Coulson, A., Dalgliesh, C., Rajan, P., Nicol, S. M., Fleming, S., et al. (2008). The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Research, 68, 7938–7946.PubMedCentralPubMed

93.

Shiota, M., Bishop, J. L., Nip, K. M., Zardan, A., Takeuchi, A., Cordonnier, T., et al. (2013). Hsp27 regulates epithelial mesenchymal transition, metastasis, and circulating tumor cells in prostate cancer. Cancer Research, 73, 3109–3119.PubMed

94.

Ni, L., Yang, C.-S., Gioeli, D., Frierson, H., Toft, D. O., & Paschal, B. M. (2010). FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Molecular and Cellular Biology, 30, 1243–1253.PubMedCentralPubMed

95.

Taneja, S. S., Ha, S., Swenson, N. K., Torra, I. P., Rome, S., Walden, P. D., et al. (2004). ART-27, an androgen receptor coactivator regulated in prostate development and cancer. The Journal of Biological Chemistry, 279, 13944–13952.PubMed

96.

Lapouge, G., Erdmann, E., Marcias, G., Jagla, M., Monge, A., Kessler, P., et al. (2007). Unexpected paracrine action of prostate cancer cells harboring a new class of androgen receptor mutation–a new paradigm for cooperation among prostate tumor cells. International Journal of Cancer, 121, 1238–1244.

97.

Jagla, M., Fève, M., Kessler, P., Lapouge, G., Erdmann, E., Serra, S., et al. (2007). A splicing variant of the androgen receptor detected in a metastatic prostate cancer exhibits exclusively cytoplasmic actions. Endocrinology, 148, 4334–4343.PubMed

98.

Dehm, S. M., & Tindall, D. J. (2011). Alternatively spliced androgen receptor variants. Endocrine-Related Cancer, 18, R183–196.PubMedCentralPubMed

99.

Guo, Z., Yang, X., Sun, F., Jiang, R., Linn, D. E., Chen, H., et al. (2009). A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Research, 69, 2305–2313.PubMedCentralPubMed

100.

Mediwala, S. N., Sun, H., Szafran, A. T., Hartig, S. M., Sonpavde, G., Hayes, T. G., et al. (2013). The activity of the androgen receptor variant AR-V7 is regulated by FOXO1 in a PTEN-PI3K-AKT-dependent way. The Prostate, 73, 267–277.PubMedCentralPubMed

101.

Watson, P. A., Chen, Y. F., Balbas, M. D., Wongvipat, J., Socci, N. D., Viale, A., et al. (2010). Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor. Proceedings of the National Academy of Sciences of the United States of America, 107, 16759–16765.PubMedCentralPubMed

102.

Hu, R., Lu, C., Mostaghel, E. A., Yegnasubramanian, S., Gurel, M., Tannahill, C., et al. (2012). Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer. Cancer Research, 72, 3457–3462.PubMedCentralPubMed

103.

Li, Y., Chan, S. C., Brand, L. J., Hwang, T. H., Silverstein, K. A. T., & Dehm, S. M. (2013). Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Research, 73, 483–489.PubMedCentralPubMed

104.

Mostaghel, E. A., Marck, B. T., Plymate, S. R., Vessella, R. L., Balk, S., Matsumoto, A. M., et al. (2011). Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants. Clinical Cancer Research, 17, 5913–5925.PubMedCentralPubMed

105.

Hörnberg, E., Ylitalo, E. B., Crnalic, S., Antti, H., Stattin, P., Widmark, A., et al. (2011). Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PloS One, 6, e19059.PubMedCentralPubMed

106.

Culig, Z., Hobisch, A., Cronauer, M. V., Radmayr, C., Trapman, J., Hittmair, A., et al. (1994). Androgen receptor activation in prostatic tumor cell lines by insulin-like growth factor-I, keratinocyte growth factor, and epidermal growth factor. Cancer Research, 54, 5474–5478.PubMed

107.

Liu, Y., Karaca, M., Zhang, Z., Gioeli, D., Earp, H. S., & Whang, Y. E. (2010). Dasatinib inhibits site-specific tyrosine phosphorylation of androgen receptor by Ack1 and Src kinases. Oncogene, 29, 3208–3216.PubMedCentralPubMed

108.

Craft, N., Shostak, Y., Carey, M., & Sawyers, C. L. (1999). A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nature Medicine, 5, 280–285.PubMed

109.

Nazareth, L. V., & Weigel, N. L. (1996). Activation of the human androgen receptor through a protein kinase A signaling pathway. The Journal of Biological Chemistry, 271, 19900–19907.PubMed

110.

Wang, G., Jones, S. J. M., Marra, M. A., & Sadar, M. D. (2006). Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene, 25, 7311–7323.PubMed

111.

Yuan, T.-C., Veeramani, S., & Lin, M.-F. (2007). Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells. Endocrine-Related Cancer, 14, 531–547.PubMed

112.

Desai, S. J., Ma, A.-H., Tepper, C. G., Chen, H.-W., & Kung, H.-J. (2006). Inappropriate activation of the androgen receptor by nonsteroids: involvement of the Src kinase pathway and its therapeutic implications. Cancer Research, 66, 10449–10459.PubMed

113.

Giri, D., Ozen, M., & Ittmann, M. (2001). Interleukin-6 is an autocrine growth factor in human prostate cancer. The American Journal of Pathology, 159, 2159–2165.PubMedCentralPubMed

114.

Culig, Z., Steiner, H., Bartsch, G., & Hobisch, A. (2005). Interleukin-6 regulation of prostate cancer cell growth. Journal of Cellular Biochemistry, 95, 497–505.PubMed

115.

Jin, R. J., Lho, Y., Connelly, L., Wang, Y., Yu, X., Saint Jean, L., et al. (2008). The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth. Cancer Research, 68, 6762–6769.PubMedCentralPubMed

116.

Ueda, T., Bruchovsky, N., & Sadar, M. D. (2002). Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways. The Journal of Biological Chemistry, 277, 7076–7085.PubMed

117.

Guo, Z., Dai, B., Jiang, T., Xu, K., Xie, Y., Kim, O., et al. (2006). Regulation of androgen receptor activity by tyrosine phosphorylation. Cancer Cell, 10, 309–319.PubMed

118.

Asim, M., Siddiqui, I. A., Hafeez, B. B., Baniahmad, A., & Mukhtar, H. (2008). Src kinase potentiates androgen receptor transactivation function and invasion of androgen-independent prostate cancer C4-2 cells. Oncogene, 27, 3596–3604.PubMed

119.

Twillie, D. A., Eisenberger, M. A., Carducci, M. A., Hseih, W. S., Kim, W. Y., & Simons, J. W. (1995). Interleukin-6: a candidate mediator of human prostate cancer morbidity. Urology, 45, 542–549.PubMed

120.

Hobisch, A., Rogatsch, H., Hittmair, A., Fuchs, D., Bartsch, G., Jr., Klocker, H., et al. (2000). Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue. The Journal of Pathology, 191, 239–244.PubMed

121.

Santer, F. R., Malinowska, K., Culig, Z., & Cavarretta, I. T. (2010). Interleukin-6 trans-signalling differentially regulates proliferation, migration, adhesion and maspin expression in human prostate cancer cells. Endocrine-Related Cancer, 17, 241–253.PubMedCentralPubMed

122.

Spiotto, M. T., & Chung, T. D. (2000). STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells. The Prostate, 42, 186–195.PubMed

123.

Malinowska, K., Neuwirt, H., Cavarretta, I. T., Bektic, J., Steiner, H., Dietrich, H., et al. (2009). Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor. Endocrine-Related Cancer, 16, 155–169.PubMed

124.

Gross, M., Liu, B., Tan, J., French, F. S., Carey, M., & Shuai, K. (2001). Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells. Oncogene, 20, 3880–3887.PubMed

125.

Hoefer, J., Schäfer, G., Klocker, H., Erb, H. H. H., Mills, I. G., Hengst, L., et al. (2012). PIAS1 is increased in human prostate cancer and enhances proliferation through inhibition of p21. The American Journal of Pathology, 180, 2097–2107.PubMed

126.

Chun, J. Y., Nadiminty, N., Dutt, S., Lou, W., Yang, J. C., Kung, H.-J., et al. (2009). Interleukin-6 regulates androgen synthesis in prostate cancer cells. Clinical Cancer Research, 15, 4815–4822.PubMedCentralPubMed

127.

Smith, P. C., & Keller, E. T. (2001). Anti-interleukin-6 monoclonal antibody induces regression of human prostate cancer xenografts in nude mice. The Prostate, 48, 47–53.PubMed

128.

Wallner, L., Dai, J., Escara-Wilke, J., Zhang, J., Yao, Z., Lu, Y., et al. (2006). Inhibition of interleukin-6 with CNTO328, an anti-interleukin-6 monoclonal antibody, inhibits conversion of androgen-dependent prostate cancer to an androgen-independent phenotype in orchiectomized mice. Cancer Research, 66, 3087–3095.PubMed

129.

Karkera, J., Steiner, H., Li, W., Skradski, V., Moser, P. L., Riethdorf, S., et al. (2011). The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a phase I study. The Prostate, 71, 1455–1465.PubMed

130.

Kreisberg, J. I., Malik, S. N., Prihoda, T. J., Bedolla, R. G., Troyer, D. A., Kreisberg, S., et al. (2004). Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Research, 64, 5232–5236.PubMed

131.

Bakin, R. E., Gioeli, D., Sikes, R. A., Bissonette, E. A., & Weber, M. J. (2003). Constitutive activation of the Ras/mitogen-activated protein kinase signaling pathway promotes androgen hypersensitivity in LNCaP prostate cancer cells. Cancer Research, 63, 1981–1989.PubMed

132.

Shu, S.-K., Liu, Q., Coppola, D., & Cheng, J. Q. (2010). Phosphorylation and activation of androgen receptor by Aurora-A. The Journal of Biological Chemistry, 285, 33045–33053.PubMedCentralPubMed

133.

Mahajan, K., Challa, S., Coppola, D., Lawrence, H., Luo, Y., Gevariya, H., et al. (2010). Effect of Ack1 tyrosine kinase inhibitor on ligand-independent androgen receptor activity. The Prostate, 70, 1274–1285.PubMedCentralPubMed

134.

Seaton, A., Scullin, P., Maxwell, P. J., Wilson, C., Pettigrew, J., Gallagher, R., et al. (2008). Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis, 29, 1148–1156.PubMed

135.

Lee, S. O., Lou, W., Hou, M., Onate, S. A., & Gao, A. C. (2003). Interleukin-4 enhances prostate-specific antigen expression by activation of the androgen receptor and Akt pathway. Oncogene, 22, 7981–7988.PubMed

136.

Korenman, S. G., & Lipsett, M. B. (1965). Direct peripheral conversion of dehydroepiandrosterone to testosterone glucuronoside. Steroids, 5, 509–517.

137.

Locke, J. A., Guns, E. S., Lubik, A. A., Adomat, H. H., Hendy, S. C., Wood, C. A., et al. (2008). Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer. Cancer Research, 68, 6407–6415.PubMed

138.

Barrie, S. E., Potter, G. A., Goddard, P. M., Haynes, B. P., Dowsett, M., & Jarman, M. (1994). Pharmacology of novel steroidal inhibitors of cytochrome P450(17) alpha (17 alpha-hydroxylase/C17-20 lyase). The Journal of Steroid Biochemistry and Molecular Biology, 50, 267–273.PubMed

139.

Attard, G., Reid, A. H. M., Yap, T. A., Raynaud, F., Dowsett, M., Settatree, S., et al. (2008). Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. Journal of Clinical Oncology, 26, 4563–4571.PubMed

140.

Danila, D. C., Morris, M. J., de Bono, J. S., Ryan, C. J., Denmeade, S. R., Smith, M. R., et al. (2010). Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer. Journal of Clinical Oncology, 28, 1496–1501.PubMedCentralPubMed

141.

Fizazi, K., Scher, H. I., Molina, A., Logothetis, C. J., Chi, K. N., Jones, R. J., et al. (2012). Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. The Lancet Oncology, 13, 983–992.PubMed

142.

Ryan, C. J., Smith, M. R., de Bono, J. S., Molina, A., Logothetis, C. J., de Souza, P., et al. (2013). Abiraterone in metastatic prostate cancer without previous chemotherapy. The New England Journal of Medicine, 368, 138–148.PubMedCentralPubMed

143.

Cai, C., Chen, S., Ng, P., Bubley, G. J., Nelson, P. S., Mostaghel, E. A., et al. (2011). Intratumoral de novo steroid synthesis activates androgen receptor in castration-resistant prostate cancer and is upregulated by treatment with CYP17A1 inhibitors. Cancer Research, 71, 6503–6513.PubMedCentralPubMed

144.

Veldscholte, J., Ris-Stalpers, C., Kuiper, G. G., Jenster, G., Berrevoets, C., Claassen, E., et al. (1990). A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochemical and Biophysical Research Communications, 173, 534–540.PubMed

145.

Tran, C., Ouk, S., Clegg, N. J., Chen, Y., Watson, P. A., Arora, V., et al. (2009). Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science, 324, 787–790.PubMedCentralPubMed

146.

Scher, H. I., Fizazi, K., Saad, F., Taplin, M.-E., Sternberg, C. N., Miller, K., et al. (2012). Increased survival with enzalutamide in prostate cancer after chemotherapy. The New England Journal of Medicine, 367, 1187–1197.PubMed

147.

Scher, H. I., Beer, T. M., Higano, C. S., Anand, A., Taplin, M.-E., Efstathiou, E., et al. (2010). Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet, 375, 1437–1446.PubMedCentralPubMed

148.

Loriot, Y., Bianchini, D., Ileana, E., Sandhu, S., Patrikidou, A., Pezaro, C., et al. (2013). Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Annals of Oncology.

149.

Handratta, V. D., Vasaitis, T. S., Njar, V. C. O., Gediya, L. K., Kataria, R., Chopra, P., et al. (2005). Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model. Journal of Medicinal Chemistry, 48, 2972–2984.PubMed

150.

Vasaitis, T., Belosay, A., Schayowitz, A., Khandelwal, A., Chopra, P., Gediya, L. K., et al. (2008). Androgen receptor inactivation contributes to antitumor efficacy of 17{alpha}-hydroxylase/17,20-lyase inhibitor 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene in prostate cancer. Molecular Cancer Therapeutics, 7, 2348–2357.PubMedCentralPubMed

151.

Clegg, N. J., Wongvipat, J., Joseph, J. D., Tran, C., Ouk, S., Dilhas, A., et al. (2012). ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Research, 72, 1494–1503.PubMedCentralPubMed

152.

Attar, R. M., Jure-Kunkel, M., Balog, A., Cvijic, M. E., Dell-John, J., Rizzo, C. A., et al. (2009). Discovery of BMS-641988, a novel and potent inhibitor of androgen receptor signaling for the treatment of prostate cancer. Cancer Research, 69, 6522–6530.PubMed

153.

Rathkopf, D., Liu, G., Carducci, M. A., Eisenberger, M. A., Anand, A., Morris, M. J., et al. (2011). Phase I dose-escalation study of the novel antiandrogen BMS-641988 in patients with castration-resistant prostate cancer. Clinical Cancer Research, 17, 880–887.PubMedCentralPubMed

154.

Kaku, T., Hitaka, T., Ojida, A., Matsunaga, N., Adachi, M., Tanaka, T., et al. (2011). Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorganic & Medicinal Chemistry, 19, 6383–6399.

155.

Yamaoka, M., Hara, T., Hitaka, T., Kaku, T., Takeuchi, T., Takahashi, J., et al. (2012). Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. The Journal of Steroid Biochemistry and Molecular Biology, 129, 115–128.PubMed

156.

Hara, T., Kouno, J., Kaku, T., Takeuchi, T., Kusaka, M., Tasaka, A., et al. (2013). Effect of a novel 17,20-lyase inhibitor, orteronel (TAK-700), on androgen synthesis in male rats. The Journal of Steroid Biochemistry and Molecular Biology, 134, 80–91.PubMed

157.

Andersen, R. J., Mawji, N. R., Wang, J., Wang, G., Haile, S., Myung, J.-K., et al. (2010). Regression of castrate-recurrent prostate cancer by a small-molecule inhibitor of the amino-terminus domain of the androgen receptor. Cancer Cell, 17, 535–546.PubMed

158.

Jenster, G., van der Korput, H. A. G. M., van Vroonhoven, C., van der Kwast, T. H., Trapman, J., & Brinkmann, A. O. (1991). Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Molecular Endocrinology, 5, 1396–1404.PubMed

159.

Fang, Y., Fliss, A. E., Robins, D. M., & Caplan, A. J. (1996). Hsp90 regulates androgen receptor hormone binding affinity in vivo. The Journal of Biological Chemistry, 271, 28697–28702.PubMed

160.

Vanaja, D. K., Mitchell, S. H., Toft, D. O., & Young, C. Y. F. (2002). Effect of geldanamycin on androgen receptor function and stability. Cell Stress & Chaperones, 7, 55–64.

161.

Heath, E. I., Hillman, D. W., Vaishampayan, U., Sheng, S., Sarkar, F., Harper, F., et al. (2008). A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clinical Cancer Research, 14, 7940–7946.PubMedCentralPubMed

162.

Oh, W. K., Galsky, M. D., Stadler, W. M., Srinivas, S., Chu, F., Bubley, G., et al. (2011). Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (ipi-504), in patients with castration-resistant prostate cancer. Urology, 78, 626–630.PubMedCentralPubMed

163.

Shafi, A. A., Cox, M. B., & Weigel, N. L. (2013). Androgen receptor splice variants are resistant to inhibitors of Hsp90 and FKBP52, which alter androgen receptor activity and expression. Steroids, 78, 548–554.PubMedCentralPubMed

164.

He, S., Zhang, C., Shafi, A. A., Sequeira, M., Acquaviva, J., Friedland, J. C., et al. (2013). Potent activity of the Hsp90 inhibitor ganetespib in prostate cancer cells irrespective of androgen receptor status or variant receptor expression. International Journal of Oncology, 42, 35–43.PubMedCentralPubMed

165.

Chou, Y.-W., Chaturvedi, N. K., Ouyang, S., Lin, F.-F., Kaushik, D., Wang, J., et al. (2011). Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells. Cancer Letters, 311, 177–186.PubMedCentralPubMed

166.

Gravina, G. L., Marampon, F., Muzi, P., Mancini, A., Piccolella, M., Negri-Cesi, P., et al. (2013). PXD101 potentiates hormonal therapy and prevents the onset of castration-resistant phenotype modulating androgen receptor, HSP90, and CRM1 in preclinical models of prostate cancer. Endocrine-Related Cancer, 20, 321–337.PubMed

167.

Iacopino, F., Urbano, R., Graziani, G., Muzi, A., Navarra, P., & Sica, G. (2008). Valproic acid activity in androgen-sensitive and -insensitive human prostate cancer cells. International Journal of Oncology, 32, 1293–1303.PubMed

168.

Welsbie, D. S., Xu, J., Chen, Y., Borsu, L., Scher, H. I., Rosen, N., et al. (2009). Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer. Cancer Research, 69, 958–966.PubMedCentralPubMed

169.

Molife, L. R., Attard, G., Fong, P. C., Karavasilis, V., Reid, A. H. M., Patterson, S., et al. (2010). Phase II, two-stage, single-arm trial of the histone deacetylase inhibitor (HDACi) romidepsin in metastatic castration-resistant prostate cancer (CRPC). Annals of Oncology, 21, 109–113.PubMed

170.

Wang, Y., Lonard, D. M., Yu, Y., Chow, D.-C., Palzkill, T. G., & O’Malley, B. W. (2011). Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1. Molecular Endocrinology, 25, 2041–2053.PubMedCentralPubMed

Title: Androgen receptor signaling in prostate cancer
Authors: Zoran Culig
Frédéric R. Santer
Publication date: 01-09-2014
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 2-3/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-013-9474-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2-3/2014

Circulating tumour cells—a bona fide cause of metastatic cancer

Mouse models of prostate cancer: picking the best model for the question

Bone-targeting agents in prostate cancer

The developing story of Sprouty and cancer

A multi-targeted approach to treating bone metastases

Insulin-like growth factor receptor-1 (IGF-IR) as a target for prostate cancer therapy

Keynote webinar | Spotlight on antibody–drug conjugates in cancer