Top

Published in:

01-12-2021 | Breast Cancer | Research article

Secreted indicators of androgen receptor activity in breast cancer pre-clinical models

Authors: Toru Hanamura, Jessica L. Christenson, Kathleen I. O’Neill, Emmanuel Rosas, Nicole S. Spoelstra, Michelle M. Williams, Jennifer K. Richer

Published in: Breast Cancer Research | Issue 1/2021

Abstract

Purpose

Accumulating evidence has attracted attention to the androgen receptor (AR) as a biomarker and therapeutic target in breast cancer. We hypothesized that AR activity within the tumor has clinical implications and investigated whether androgen responsive serum factors might serve as a minimally invasive indicator of tumor AR activity.

Methods

Based on a comprehensive gene expression analysis of an AR-positive, triple negative breast cancer patient-derived xenograft (PDX) model, 163 dihydrotestosterone (DHT)-responsive genes were defined as an androgen responsive gene set. Among them, we focused on genes that were DHT-responsive that encode secreted proteins, namely KLK3, AZGP1 and PIP, that encode the secreted factors prostate specific antigen (PSA), zinc-alpha-2-glycoprotein (ZAG) and prolactin induced protein (PIP), respectively. Using AR-positive breast cancer cell lines representing all breast cancer subtypes, expression of candidate factors was assessed in response to agonist DHT and antagonist enzalutamide. Gene set enrichment analysis (GSEA) was performed on publically available gene expression datasets from breast cancer patients to analyze the relationship between genes encoding the secreted factors and other androgen responsive gene sets in each breast cancer subtype.

Results

Anti-androgen treatment decreased proliferation in all cell lines tested representing various tumor subtypes. Expression of the secreted factors was regulated by AR activation in the majority of breast cancer cell lines. In GSEA, the candidate genes were positively correlated with an androgen responsive gene set across breast cancer subtypes.

Conclusion

KLK3, AZGP1 and PIP are AR regulated and reflect tumor AR activity. Further investigations are needed to examine the potential efficacy of these factors as serum biomarkers.

Available only for authorised users

Libson S, Lippman M. A review of clinical aspects of breast cancer. Int Rev Psychiatry (Abingdon, England). 2014;26(1):4–15. https://doi.org/10.3109/09540261.2013.852971.CrossRef

Abdelwahab Yousef AJ. Male Breast cancer: epidemiology and risk factors. Semin Oncol. 2017;44(4):267–72. https://doi.org/10.1053/j.seminoncol.2017.11.002.CrossRefPubMed

Harbeck N, Gnant M. Breast cancer. Lancet (London, England). 2017;389(10074):1134–50. https://doi.org/10.1016/s0140-6736(16)31891-8.CrossRef

Gnant M, Harbeck N, Thomssen C. St. Gallen/Vienna 2017: a brief summary of the consensus discussion about escalation and de-escalation of primary breast cancer treatment. Breast Care (Basel, Switzerland). 2017;12(2):102–7. https://doi.org/10.1159/000475698.CrossRef

Clarke R, Leonessa F, Welch JN, Skaar TC. Cellular and molecular pharmacology of antiestrogen action and resistance. Pharmacol Rev. 2001;53(1):25–71.PubMed

Loibl S, Gianni L. HER2-positive breast cancer. Lancet (London, England). 2017;389(10087):2415–29. https://doi.org/10.1016/s0140-6736(16)32417-5.CrossRef

Hanamura T, Hayashi SI. Overcoming aromatase inhibitor resistance in breast cancer: possible mechanisms and clinical applications. Breast Cancer (Tokyo, Japan). 2017. https://doi.org/10.1007/s12282-017-0772-1.CrossRef

Vasiliou SK, Diamandis EP. Androgen receptor: a promising therapeutic target in breast cancer. Crit Rev Clin Lab Sci. 2019. https://doi.org/10.1080/10408363.2019.1575643.CrossRefPubMed

Collins LC, Cole KS, Marotti JD, Hu R, Schnitt SJ, Tamimi RM. Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses’ Health Study. Mod Pathol. 2011;24(7):924–31. https://doi.org/10.1038/modpathol.2011.54.CrossRefPubMedPubMedCentral

10.

Hu R, Dawood S, Holmes MD, Collins LC, Schnitt SJ, Cole K, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011;17(7):1867–74. https://doi.org/10.1158/1078-0432.Ccr-10-2021.CrossRefPubMedPubMedCentral

11.

Park S, Koo JS, Kim MS, Park HS, Lee JS, Lee JS, et al. Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol. 2011;22(8):1755–62. https://doi.org/10.1093/annonc/mdq678.CrossRefPubMed

12.

Cochrane DR, Bernales S, Jacobsen BM, Cittelly DM, Howe EN, D’Amato NC, et al. Role of the androgen receptor in breast cancer and preclinical analysis of enzalutamide. Breast Cancer Res BCR. 2014;16(1):R7. https://doi.org/10.1186/bcr3599.CrossRefPubMed

13.

Fujii R, Hanamura T, Suzuki T, Gohno T, Shibahara Y, Niwa T, et al. Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma. J Steroid Biochem Mol Biol. 2014;144(Pt B):513–22. https://doi.org/10.1016/j.jsbmb.2014.08.019.CrossRefPubMed

14.

De Amicis F, Thirugnansampanthan J, Cui Y, Selever J, Beyer A, Parra I, et al. Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells. Breast Cancer Res Treat. 2010;121(1):1–11. https://doi.org/10.1007/s10549-009-0436-8.CrossRefPubMed

15.

Basile D, Cinausero M, Iacono D, Pelizzari G, Bonotto M, Vitale MG, et al. Androgen receptor in estrogen receptor positive breast cancer: Beyond expression. Cancer Treat Rev. 2017;61:15–22. https://doi.org/10.1016/j.ctrv.2017.09.006.CrossRefPubMed

16.

D’Amato NC, Gordon MA, Babbs B, Spoelstra NS, Carson Butterfield KT, Torkko KC, et al. Cooperative dynamics of AR and ER activity in breast cancer. Mol Cancer Res MCR. 2016;14(11):1054–67. https://doi.org/10.1158/1541-7786.mcr-16-0167.CrossRefPubMed

17.

Hickey TE, Robinson JL, Carroll JS, Tilley WD. Minireview: the androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene? Mol Endocrinol (Baltimore, Md). 2012;26(8):1252–67. https://doi.org/10.1210/me.2012-1107.CrossRef

18.

Williams MM, Spoelstra NS, Arnesen S, O’Neill KI, Christenson JL, Reese J, et al. Steroid hormone receptor and infiltrating immune cell status reveals therapeutic vulnerabilities of ESR1-mutant breast cancer. Can Res. 2021;81(3):732–46. https://doi.org/10.1158/0008-5472.Can-20-1200.CrossRef

19.

Barton VN, Christenson JL, Gordon MA, Greene LI, Rogers TJ, Butterfield K, et al. Androgen receptor supports an anchorage-independent, cancer stem cell-like population in triple-negative breast cancer. Can Res. 2017;77(13):3455–66. https://doi.org/10.1158/0008-5472.can-16-3240.CrossRef

20.

Barton VN, D’Amato NC, Gordon MA, Lind HT, Spoelstra NS, Babbs BL, et al. Multiple molecular subtypes of triple-negative breast cancer critically rely on androgen receptor and respond to enzalutamide in vivo. Mol Cancer Ther. 2015;14(3):769–78. https://doi.org/10.1158/1535-7163.mct-14-0926.CrossRefPubMedPubMedCentral

21.

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Investig. 2011;121(7):2750–67. https://doi.org/10.1172/jci45014.CrossRefPubMedPubMedCentral

22.

Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, et al. Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell. 2011;20(1):119–31. https://doi.org/10.1016/j.ccr.2011.05.026.CrossRefPubMedPubMedCentral

23.

Barton VN, Gordon MA, Richer JK, Elias A. Anti-androgen therapy in triple-negative breast cancer. Ther Adv Med Oncol. 2016;8(4):305–8. https://doi.org/10.1177/1758834016646735.CrossRefPubMedPubMedCentral

24.

Krop I, Abramson V, Colleoni M, Traina T, Holmes F, Estevez L, et al. Abstract GS4–07: Results from a randomized placebo-controlled phase 2 trial evaluating exemestane ± enzalutamide in patients with hormone receptor–positive breast cancer. Cancer Res. 2018;78(4 Supplement):GS4-07-GS4. https://doi.org/10.1158/1538-7445.Sabcs17-gs4-07.CrossRef

25.

Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin Cancer Res. 2013;19(19):5505–12. https://doi.org/10.1158/1078-0432.Ccr-12-3327.CrossRefPubMedPubMedCentral

26.

Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O’Shaughnessy J, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer. J Clin Oncol. 2018;36(9):884–90. https://doi.org/10.1200/jco.2016.71.3495.CrossRefPubMedPubMedCentral

27.

Traina TA, Miller K, Yardley DA, O’Shaughnessy J, Cortes J, Awada A, et al. Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC). J Clin Oncol. 2015;33(15_suppl):1003. https://doi.org/10.1200/jco.2015.33.15_suppl.1003.CrossRef

28.

Okano M, Oshi M, Butash AL, Asaoka M, Katsuta E, Peng X, et al. Estrogen receptor positive breast cancer with high expression of androgen receptor has less cytolytic activity and worse response to neoadjuvant chemotherapy but better survival. Int J Mol Sci. 2019;20(11):2655. https://doi.org/10.3390/ijms20112655.CrossRefPubMedCentral

29.

Asano Y, Kashiwagi S, Onoda N, Kurata K, Morisaki T, Noda S, et al. Clinical verification of sensitivity to preoperative chemotherapy in cases of androgen receptor-expressing positive breast cancer. Br J Cancer. 2016;114(1):14–20. https://doi.org/10.1038/bjc.2015.434.CrossRefPubMedPubMedCentral

30.

Masuda H, Baggerly KA, Wang Y, Zhang Y, Gonzalez-Angulo AM, Meric-Bernstam F, et al. Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res. 2013;19(19):5533–40. https://doi.org/10.1158/1078-0432.Ccr-13-0799.CrossRefPubMed

31.

Kono M, Fujii T, Lim B, Karuturi MS, Tripathy D, Ueno NT. Androgen receptor function and androgen receptor-targeted therapies in breast cancer: a review. JAMA Oncol. 2017;3(9):1266–73. https://doi.org/10.1001/jamaoncol.2016.4975.CrossRefPubMed

32.

Christenson JL, O’Neill KI, Williams MM, Spoelstra NS, Jones KL, Trahan GD, et al. Activity of combined androgen receptor antagonism and cell cycle inhibition in androgen receptor-positive triple-negative breast cancer. Mol Cancer Ther. 2021. https://doi.org/10.1158/1535-7163.Mct-20-0807.CrossRefPubMed

33.

DeRose YS, Wang G, Lin YC, Bernard PS, Buys SS, Ebbert MT, et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat Med. 2011;17(11):1514–20. https://doi.org/10.1038/nm.2454.CrossRefPubMedPubMedCentral

34.

Rosas E, Roberts JT, O’Neill KI, Christenson JL, Williams MM, Hanamura T, et al. A positive feedback loop between TGFβ and androgen receptor supports triple-negative breast cancer anoikis resistance. Endocrinology. 2021. https://doi.org/10.1210/endocr/bqaa226.CrossRefPubMed

35.

Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res BCR. 2011;13(4):215. https://doi.org/10.1186/bcr2889.CrossRefPubMed

36.

Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4. https://doi.org/10.1158/2159-8290.cd-12-0095.CrossRefPubMed

37.

Koboldt DC, Fulton R, McLellan M, Schmidt H, Kalicki-Veizer J, McMichael J, Fulton L, Dooling D, Ding L, Mardis E, Wilson R. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70. https://doi.org/10.1038/nature11412.CrossRef

38.

Brueffer C, Vallon-Christersson J, Grabau D, Ehinger A, Häkkinen J, Hegardt C, et al. Clinical value of RNA sequencing-based classifiers for prediction of the five conventional breast cancer biomarkers: a report from the population-based Multicenter Sweden Cancerome Analysis Network—breast initiative. JCO Precis Oncol. 2018. https://doi.org/10.1200/po.17.00135.CrossRefPubMedPubMedCentral

39.

Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73. https://doi.org/10.1038/ng1180.CrossRef

40.

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102(43):15545–50. https://doi.org/10.1073/pnas.0506580102.CrossRefPubMedPubMedCentral

41.

Chen X, Li J, Gray WH, Lehmann BD, Bauer JA, Shyr Y, et al. TNBCtype: a subtyping tool for triple-negative breast cancer. Cancer Inform. 2012;11:147–56. https://doi.org/10.4137/cin.S9983.CrossRefPubMedPubMedCentral

42.

Ziegler YS, Moresco JJ, Yates JR 3rd, Nardulli AM. Integration of breast cancer secretomes with clinical data elucidates potential serum markers for disease detection, diagnosis, and prognosis. PLoS ONE. 2016;11(6): e0158296. https://doi.org/10.1371/journal.pone.0158296.CrossRefPubMedPubMedCentral

43.

Hall RE, Birrell SN, Tilley WD, Sutherland RL. MDA-MB-453, an androgen-responsive human breast carcinoma cell line with high level androgen receptor expression. Eur J Cancer (Oxford, England: 1990). 1994;30a(4):484–90. https://doi.org/10.1016/0959-8049(94)90424-3.CrossRef

44.

Cleutjens KB, van der Korput HA, van Eekelen CC, van Rooij HC, Faber PW, Trapman J. An androgen response element in a far upstream enhancer region is essential for high, androgen-regulated activity of the prostate-specific antigen promoter. Mol Endocrinol (Baltimore, Md). 1997;11(2):148–61. https://doi.org/10.1210/mend.11.2.9883.CrossRef

45.

Cao R, Ke M, Wu Q, Tian Q, Liu L, Dai Z, et al. AZGP1 is androgen responsive and involved in AR-induced prostate cancer cell proliferation and metastasis. J Cell Physiol. 2019;234(10):17444–58. https://doi.org/10.1002/jcp.28366.CrossRefPubMed

46.

Baniwal SK, Little GH, Chimge NO, Frenkel B. Runx2 controls a feed-forward loop between androgen and prolactin-induced protein (PIP) in stimulating T47D cell proliferation. J Cell Physiol. 2012;227(5):2276–82. https://doi.org/10.1002/jcp.22966.CrossRefPubMedPubMedCentral

47.

Dutertre M, Gratadou L, Dardenne E, Germann S, Samaan S, Lidereau R, et al. Estrogen regulation and physiopathologic significance of alternative promoters in breast cancer. Can Res. 2010;70(9):3760–70. https://doi.org/10.1158/0008-5472.can-09-3988.CrossRef

48.

Novel agents show promise against acquired endocrine resistance in ER+ advanced breast cancer. Oncologist. 2021;26(Suppl 3):S15–S6 doi https://doi.org/10.1002/onco.13874.

49.

Black MH, Giai M, Ponzone R, Sismondi P, Yu H, Diamandis EP. Serum total and free prostate-specific antigen for breast cancer diagnosis in women. Clin Cancer Res. 2000;6(2):467–73.PubMed

50.

Bundred NJ, Scott WN, Davies SJ, Miller WR, Mansel RE. Zinc alpha-2 glycoprotein levels in serum and breast fluids: a potential marker of apocrine activity. Eur J Cancer (Oxford, England: 1990). 1991;27(5):549–52. https://doi.org/10.1016/0277-5379(91)90213-w.CrossRef

51.

Haagensen DE Jr, Kister SJ, Panick J, Giannola J, Hansen HJ, Wells SA Jr. Comparative evaluation of carcinoembryonic antigen and gross cystic disease fluid protein as plasma markers for human breast carcinoma. Cancer. 1978;42(3 Suppl):1646–52. https://doi.org/10.1002/1097-0142(197809)42:3+%3c1646::aid-cncr2820420844%3e3.0.co;2-n.CrossRefPubMed

52.

Hanamura T, Ohno K, Hokibara S, Murasawa H, Nakamura T, Watanabe H, et al. Clinical significance of serum PSA in breast cancer patients. BMC Cancer. 2019;19(1):1021. https://doi.org/10.1186/s12885-019-6256-2.CrossRefPubMedPubMedCentral

53.

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738–48. https://doi.org/10.1056/NEJMoa1609709.CrossRefPubMed

54.

Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J. Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem. 1996;271(11):6379–88.CrossRef

55.

Perez-Ibave DC, Burciaga-Flores CH, Elizondo-Riojas MA. Prostate-specific antigen (PSA) as a possible biomarker in non-prostatic cancer: a review. Cancer Epidemiol. 2018;54:48–55. https://doi.org/10.1016/j.canep.2018.03.009.CrossRefPubMed

56.

Magklara A, Grass L, Diamandis EP. Differential steroid hormone regulation of human glandular kallikrein (hK2) and prostate-specific antigen (PSA) in breast cancer cell lines. Breast Cancer Res Treat. 2000;59(3):263–70.CrossRef

57.

Yu H, Diamandis EP, Zarghami N, Grass L. Induction of prostate specific antigen production by steroids and tamoxifen in breast cancer cell lines. Breast Cancer Res Treat. 1994;32(3):291–300. https://doi.org/10.1007/bf00666006.CrossRefPubMed

58.

Zarghami N, Grass L, Diamandis EP. Steroid hormone regulation of prostate-specific antigen gene expression in breast cancer. Br J Cancer. 1997;75(4):579–88.CrossRef

59.

Chalbos D, Haagensen D, Parish T, Rochefort H. Identification and androgen regulation of two proteins released by T47D human breast cancer cells. Can Res. 1987;47(11):2787–92.

60.

Lopez-Boado YS, Diez-Itza I, Tolivia J, Lopez-Otin C. Glucocorticoids and androgens up-regulate the Zn-alpha 2-glycoprotein messenger RNA in human breast cancer cells. Breast Cancer Res Treat. 1994;29(3):247–58. https://doi.org/10.1007/bf00666478.CrossRefPubMed

61.

Dumont M, Dauvois S, Simard J, Garcia T, Schachter B, Labrie F. Antagonism between estrogens and androgens on GCDFP-15 gene expression in ZR-75-1 cells and correlation between GCDFP-15 and estrogen as well as progesterone receptor expression in human breast cancer. J Steroid Biochem. 1989;34(1–6):397–402. https://doi.org/10.1016/0022-4731(89)90115-5.CrossRefPubMed

62.

Simard J, Hatton AC, Labrie C, Dauvois S, Zhao HF, Haagensen DE, et al. Inhibitory effect of estrogens on GCDFP-15 mRNA levels and secretion in ZR-75-1 human breast cancer cells. Mol Endocrinol (Baltimore, Md). 1989;3(4):694–702. https://doi.org/10.1210/mend-3-4-694.CrossRef

63.

Smith R, Liu M, Liby T, Bayani N, Bucher E, Chiotti K, et al. Enzalutamide response in a panel of prostate cancer cell lines reveals a role for glucocorticoid receptor in enzalutamide resistant disease. Sci Rep. 2020;10(1):21750. https://doi.org/10.1038/s41598-020-78798-x.CrossRefPubMedPubMedCentral

64.

Doane AS, Danso M, Lal P, Donaton M, Zhang L, Hudis C, et al. An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen. Oncogene. 2006;25(28):3994–4008. https://doi.org/10.1038/sj.onc.1209415.CrossRefPubMed

65.

Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, et al. Identification of molecular apocrine breast tumours by microarray analysis. Oncogene. 2005;24(29):4660–71. https://doi.org/10.1038/sj.onc.1208561.CrossRefPubMed

66.

Baniwal SK, Chimge NO, Jordan VC, Tripathy D, Frenkel B. Prolactin-induced protein (PIP) regulates proliferation of luminal A type breast cancer cells in an estrogen-independent manner. PLoS ONE. 2014;8(6): e62361. https://doi.org/10.1371/journal.pone.0062361.CrossRefPubMed

67.

Bleach R, McIlroy M. The divergent function of androgen receptor in breast cancer; analysis of steroid mediators and tumor intracrinology. Front Endocrinol. 2018;9:594. https://doi.org/10.3389/fendo.2018.00594.CrossRef

68.

Sasano H, Suzuki T, Miki Y, Moriya T. Intracrinology of estrogens and androgens in breast carcinoma. J Steroid Biochem Mol Biol. 2008;108(3–5):181–5. https://doi.org/10.1016/j.jsbmb.2007.09.012.CrossRefPubMed

69.

Panet-Raymond V, Gottlieb B, Beitel LK, Pinsky L, Trifiro MA. Interactions between androgen and estrogen receptors and the effects on their transactivational properties. Mol Cell Endocrinol. 2000;167(1–2):139–50.CrossRef

70.

Peters AA, Buchanan G, Ricciardelli C, Bianco-Miotto T, Centenera MM, Harris JM, et al. Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer. Can Res. 2009;69(15):6131–40. https://doi.org/10.1158/0008-5472.CAN-09-0452.CrossRef

71.

Poulin R, Simard J, Labrie C, Petitclerc L, Dumont M, Lagace L, et al. Down-regulation of estrogen receptors by androgens in the ZR-75-1 human breast cancer cell line. Endocrinology. 1989;125(1):392–9. https://doi.org/10.1210/endo-125-1-392.CrossRefPubMed

72.

Rao AR, Motiwala HG, Karim OM. The discovery of prostate-specific antigen. BJU Int. 2008;101(1):5–10. https://doi.org/10.1111/j.1464-410X.2007.07138.x.CrossRefPubMed

73.

Mannello F, Gazzanelli G. Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics? Breast Cancer Res BCR. 2001;3(4):238–43.CrossRef

74.

Black MH, Diamandis EP. The diagnostic and prognostic utility of prostate-specific antigen for diseases of the breast. Breast Cancer Res Treat. 2000;59(1):1–14.CrossRef

75.

Hautmann S, Huland E, Grupp C, Haese A, Huland H. Super-sensitive prostate-specific antigen (PSA) in serum of women with benign breast disease or breast cancer. Anticancer Res. 2000;20(3b):2151–4.PubMed

76.

Bundred NJ, Miller WR, Walker RA. An immunohistochemical study of the tissue distribution of the breast cyst fluid protein, zinc alpha 2 glycoprotein. Histopathology. 1987;11(6):603–10. https://doi.org/10.1111/j.1365-2559.1987.tb02670.x.CrossRefPubMed

77.

Diez-Itza I, Sanchez LM, Allende MT, Vizoso F, Ruibal A, Lopez-Otin C. Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. Eur J Cancer (Oxford, England: 1990). 1993;29A(9):1256–60. https://doi.org/10.1016/0959-8049(93)90068-q.CrossRef

78.

Freije JP, Fueyo A, Uria J, Lopez-Otin C. Human Zn-alpha 2-glycoprotein cDNA cloning and expression analysis in benign and malignant breast tissues. FEBS Lett. 1991;290(1–2):247–9. https://doi.org/10.1016/0014-5793(91)81271-9.CrossRefPubMed

79.

Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad F. Zinc alpha 2-glycoprotein: a multidisciplinary protein. Mol Cancer Res MCR. 2008;6(6):892–906. https://doi.org/10.1158/1541-7786.mcr-07-2195.CrossRefPubMed

80.

Fiel MI, Cernaianu G, Burstein DE, Batheja N. Value of GCDFP-15 (BRST-2) as a specific immunocytochemical marker for breast carcinoma in cytologic specimens. Acta Cytol. 1996;40(4):637–41. https://doi.org/10.1159/000333931.CrossRefPubMed

81.

Le Doussal V, Zangerle PF, Collette J, Spyratos F, Hacene K, Briere M, et al. Immunohistochemistry of a component protein of the breast cystic disease fluid with mol. wt 15,000. Eur J Cancer Clin Oncol. 1985;21(6):715–25. https://doi.org/10.1016/0277-5379(85)90269-x.CrossRefPubMed

82.

Murphy LC, Lee-Wing M, Goldenberg GJ, Shiu RP. Expression of the gene encoding a prolactin-inducible protein by human breast cancers in vivo: correlation with steroid receptor status. Can Res. 1987;47(15):4160–4.

83.

Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT. Gross cystic disease fluid protein-15 as a marker for breast cancer: immunohistochemical analysis of 690 human neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989;20(3):281–7. https://doi.org/10.1016/0046-8177(89)90137-8.CrossRefPubMed

84.

Gangadharan A, Nyirenda T, Patel K, Jaimes-Delgadillo N, Coletta D, Tanaka T, et al. Prolactin Induced Protein (PIP) is a potential biomarker for early stage and malignant breast cancer. Breast (Edinburgh, Scotland). 2018;39:101–9. https://doi.org/10.1016/j.breast.2018.03.015.CrossRef

85.

Haagensen DE Jr, Mazoujian G, Dilley WG, Pedersen CE, Kister SJ, Wells SA Jr. Breast gross cystic disease fluid analysis. I. Isolation and radioimmunoassay for a major component protein. J Natl Cancer Inst. 1979;62(2):239–47.PubMed

86.

Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer. Nat Rev Dis Primers. 2019;5(1):66. https://doi.org/10.1038/s41572-019-0111-2.CrossRefPubMed

87.

Abreu M, Cabezas-Sainz P, Pereira-Veiga T, Falo C, Abalo A, Morilla I, et al. Looking for a better characterization of triple-negative breast cancer by means of circulating tumor cells. J Clin Med. 2020. https://doi.org/10.3390/jcm9020353.CrossRefPubMedPubMedCentral

88.

Krawczyk N, Neubacher M, Meier-Stiegen F, Neubauer H, Niederacher D, Ruckhäberle E, et al. Determination of the androgen receptor status of circulating tumour cells in metastatic breast cancer patients. BMC Cancer. 2019;19(1):1101. https://doi.org/10.1186/s12885-019-6323-8.CrossRefPubMedPubMedCentral

89.

de Kruijff IE, Sieuwerts AM, Onstenk W, Jager A, Hamberg P, de Jongh FE, et al. Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer. Int J Cancer. 2019;145(4):1083–9. https://doi.org/10.1002/ijc.32209.CrossRefPubMed

90.

Aceto N, Bardia A, Wittner BS, Donaldson MC, O’Keefe R, Engstrom A, et al. AR expression in breast cancer CTCs associates with bone metastases. Mol Cancer Res MCR. 2018;16(4):720–7. https://doi.org/10.1158/1541-7786.Mcr-17-0480.CrossRefPubMed

91.

Keup C, Benyaa K, Hauch S, Sprenger-Haussels M, Tewes M, Mach P, et al. Targeted deep sequencing revealed variants in cell-free DNA of hormone receptor-positive metastatic breast cancer patients. Cell Mol Life Sci CMLS. 2020;77(3):497–509. https://doi.org/10.1007/s00018-019-03189-z.CrossRefPubMed

92.

Trigunaite A, Dimo J, Jorgensen TN. Suppressive effects of androgens on the immune system. Cell Immunol. 2015;294(2):87–94. https://doi.org/10.1016/j.cellimm.2015.02.004.CrossRefPubMed

93.

Hassan MI, Waheed A, Yadav S, Singh TP, Ahmad F. Prolactin inducible protein in cancer, fertility and immunoregulation: structure, function and its clinical implications. Cell Mol Life Sci CMLS. 2009;66(3):447–59. https://doi.org/10.1007/s00018-008-8463-x.CrossRefPubMed

94.

Hassan MI, Bilgrami S, Kumar V, Singh N, Yadav S, Kaur P, et al. Crystal structure of the novel complex formed between zinc alpha2-glycoprotein (ZAG) and prolactin-inducible protein (PIP) from human seminal plasma. J Mol Biol. 2008;384(3):663–72. https://doi.org/10.1016/j.jmb.2008.09.072.CrossRefPubMed

Title: Secreted indicators of androgen receptor activity in breast cancer pre-clinical models
Authors: Toru Hanamura
Jessica L. Christenson
Kathleen I. O’Neill
Emmanuel Rosas
Nicole S. Spoelstra
Michelle M. Williams
Jennifer K. Richer
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Stanolone
Androgens
Enzalutamide
Published in: Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-021-01478-9

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

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Oestrogen deprivation induces chemokine production and immune cell recruitment in in vitro and in vivo models of oestrogen receptor-positive breast cancer

IOERT versus external beam electrons for boost radiotherapy in stage I/II breast cancer: 10-year results of a phase III randomized study

Transcriptome analysis of heterogeneity in mouse model of metastatic breast cancer

Sole adjuvant intraoperative breast radiotherapy in Taiwan: a single-center experience

STAT5 is activated in macrophages by breast cancer cell-derived factors and regulates macrophage function in the tumor microenvironment

Regulatory T lymphocyte infiltration in metastatic breast cancer—an independent prognostic factor that changes with tumor progression

Keynote webinar | Spotlight on antibody–drug conjugates in cancer