Skip to main content
Top
Published in: Endocrine 1/2013

01-02-2013 | Original Article

The expression and actions of androgen receptor in upper urinary tract urothelial carcinoma (UUTUC) tissues and the primary cultured cells

Authors: Chih-Rong Shyr, Chi-Cheng Chen, Teng-Fu Hsieh, Chao-Hsiang Chang, Wen-Lung Ma, Shuyuan Yeh, Edward Messing, Tsung-Heng Li, Fu-Yin Li, Chawnshang Chang

Published in: Endocrine | Issue 1/2013

Login to get access

Abstract

Sex hormone receptors, androgen receptor (AR) and estrogen receptors (ERs) including both ERα and ERβ, mediate the actions of sex hormones. In this study, we aimed to evaluate sex hormone receptors expression in upper urinary tract urothelial carcinomas (UUTUCs) of ureter and renal pelvis with different tumor stages and grades as well as their possible roles in tumor progression. Immunohistochemistry was used to assay the expression of AR and ERs in the primary UUTUCs. XTT viability test was applied to evaluate cell responses for anticancer drug treatment. Wound healing assay was performed to determine cell migration abilities. AR and ERβ immunoreactivities were observed in both UUTUCs, but ERα was not detected in either UUTUCs. In UUTUC of ureter specimens, higher AR expression was found in superficial or lower grade tumors. In contrast, little difference of ERβ expression was found in superficial versus muscle-invasive tumor stages or low grades versus high grades in UUTUCs of ureter specimens. Furthermore in the primary cultured cells from UUTUC specimens, the addition of functional AR reduced cell chemosensitivity, but increased cell migration. These results provide the first data showing the expression patterns of sex hormone receptors in both renal pelvis and ureter UUTUCs. From results, we concluded that there is a positive correlation for higher AR expression found in superficial or low-grade UUTUCs of ureter and identified the functional roles of AR in UUTUC progression.
Literature
1.
2.
go back to reference Z. Kirkali, E. Tuzel, Transitional cell carcinoma of the ureter and renal pelvis. Crit. Rev. Oncol. Hematol. 47, 155–169 (2003)PubMedCrossRef Z. Kirkali, E. Tuzel, Transitional cell carcinoma of the ureter and renal pelvis. Crit. Rev. Oncol. Hematol. 47, 155–169 (2003)PubMedCrossRef
3.
go back to reference W. Oosterlinck, E. Solsona, A.P. van der Meijden, R. Sylvester, A. Bohle et al., EAU guidelines on diagnosis and treatment of upper urinary tract transitional cell carcinoma. Eur. Urol. 46, 147–154 (2004)PubMedCrossRef W. Oosterlinck, E. Solsona, A.P. van der Meijden, R. Sylvester, A. Bohle et al., EAU guidelines on diagnosis and treatment of upper urinary tract transitional cell carcinoma. Eur. Urol. 46, 147–154 (2004)PubMedCrossRef
4.
go back to reference J. Krogh, E. Kvist, B. Rye, Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences. Br. J. Urol. 67, 32–36 (1991)PubMedCrossRef J. Krogh, E. Kvist, B. Rye, Transitional cell carcinoma of the upper urinary tract: prognostic variables and post-operative recurrences. Br. J. Urol. 67, 32–36 (1991)PubMedCrossRef
5.
go back to reference J. Lehmann, H. Suttmann, I. Kovac, M. Hack, J. Kamradt et al., Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival. Eur. Urol. 51, 1281–1288 (2007)PubMedCrossRef J. Lehmann, H. Suttmann, I. Kovac, M. Hack, J. Kamradt et al., Transitional cell carcinoma of the ureter: prognostic factors influencing progression and survival. Eur. Urol. 51, 1281–1288 (2007)PubMedCrossRef
6.
go back to reference K.M. Sanderson, J. Cai, G. Miranda, D.G. Skinner, J.P. Stein, Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup. J. Urol. 177, 2088–2094 (2007)PubMedCrossRef K.M. Sanderson, J. Cai, G. Miranda, D.G. Skinner, J.P. Stein, Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup. J. Urol. 177, 2088–2094 (2007)PubMedCrossRef
7.
go back to reference M.C. Hall, S. Womack, A.I. Sagalowsky, T. Carmody, M.D. Erickstad et al., Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 52, 594–601 (1998)PubMedCrossRef M.C. Hall, S. Womack, A.I. Sagalowsky, T. Carmody, M.D. Erickstad et al., Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology 52, 594–601 (1998)PubMedCrossRef
8.
go back to reference C.H. Kang, T.J. Yu, H.H. Hsieh, J.W. Yang, K. Shu et al., The development of bladder tumors and contralateral upper urinary tract tumors after primary transitional cell carcinoma of the upper urinary tract. Cancer 98, 1620–1626 (2003)PubMedCrossRef C.H. Kang, T.J. Yu, H.H. Hsieh, J.W. Yang, K. Shu et al., The development of bladder tumors and contralateral upper urinary tract tumors after primary transitional cell carcinoma of the upper urinary tract. Cancer 98, 1620–1626 (2003)PubMedCrossRef
9.
go back to reference R.E. Zigeuner, G. Hutterer, T. Chromecki, P. Rehak, C. Langner, Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int. 98, 1181–1186 (2006)PubMedCrossRef R.E. Zigeuner, G. Hutterer, T. Chromecki, P. Rehak, C. Langner, Bladder tumour development after urothelial carcinoma of the upper urinary tract is related to primary tumour location. BJU Int. 98, 1181–1186 (2006)PubMedCrossRef
10.
go back to reference J.W. Catto, D.R. Yates, I. Rehman, A.R. Azzouzi, J. Patterson et al., Behavior of urothelial carcinoma with respect to anatomical location. J. Urol. 177, 1715–1720 (2007)PubMedCrossRef J.W. Catto, D.R. Yates, I. Rehman, A.R. Azzouzi, J. Patterson et al., Behavior of urothelial carcinoma with respect to anatomical location. J. Urol. 177, 1715–1720 (2007)PubMedCrossRef
11.
go back to reference J.W. Catto, A.R. Azzouzi, N. Amira, I. Rehman, K.M. Feeley et al., Distinct patterns of microsatellite instability are seen in tumours of the urinary tract. Oncogene 22, 8699–8706 (2003)PubMedCrossRef J.W. Catto, A.R. Azzouzi, N. Amira, I. Rehman, K.M. Feeley et al., Distinct patterns of microsatellite instability are seen in tumours of the urinary tract. Oncogene 22, 8699–8706 (2003)PubMedCrossRef
12.
go back to reference R. Zigeuner, K. Pummer, Urothelial carcinoma of the upper urinary tract: surgical approach and prognostic factors. Eur. Urol. 53, 720–731 (2008)PubMedCrossRef R. Zigeuner, K. Pummer, Urothelial carcinoma of the upper urinary tract: surgical approach and prognostic factors. Eur. Urol. 53, 720–731 (2008)PubMedCrossRef
13.
go back to reference J.J. Munoz, L.M. Ellison, Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J. Urol. 164, 1523–1525 (2000)PubMedCrossRef J.J. Munoz, L.M. Ellison, Upper tract urothelial neoplasms: incidence and survival during the last 2 decades. J. Urol. 164, 1523–1525 (2000)PubMedCrossRef
14.
go back to reference M. McGrath, D.S. Michaud, I. De Vivo, Hormonal and reproductive factors and the risk of bladder cancer in women. Am. J. Epidemiol. 163, 236–244 (2006)PubMedCrossRef M. McGrath, D.S. Michaud, I. De Vivo, Hormonal and reproductive factors and the risk of bladder cancer in women. Am. J. Epidemiol. 163, 236–244 (2006)PubMedCrossRef
15.
go back to reference H. Fajkovic, J.A. Halpern, E.K. Cha, A. Bahadori, T.F. Chromecki et al., Impact of gender on bladder cancer incidence, staging, and prognosis. World J. Urol. 29, 457–463 (2011)PubMedCrossRef H. Fajkovic, J.A. Halpern, E.K. Cha, A. Bahadori, T.F. Chromecki et al., Impact of gender on bladder cancer incidence, staging, and prognosis. World J. Urol. 29, 457–463 (2011)PubMedCrossRef
16.
go back to reference D. Mangelsdorf, C. Thummel, M. Beato, P. Herrlich, G. Schutz et al., The nuclear receptor superfamily: the second decade. Cell 83, 835–839 (1995)PubMedCrossRef D. Mangelsdorf, C. Thummel, M. Beato, P. Herrlich, G. Schutz et al., The nuclear receptor superfamily: the second decade. Cell 83, 835–839 (1995)PubMedCrossRef
17.
go back to reference G. Pelletier, Localization of androgen and estrogen receptors in rat and primate tissues. Histol. Histopathol. 15, 1261–1270 (2000)PubMed G. Pelletier, Localization of androgen and estrogen receptors in rat and primate tissues. Histol. Histopathol. 15, 1261–1270 (2000)PubMed
18.
go back to reference K.M. Rau, Y.J. Chen, M.T. Sun, H.Y. Kang, Prognostic effects and regulation of activin A, maspin, and the androgen receptor in upper urinary tract urothelial carcinoma. Anticancer Res. 31, 1713–1720 (2011)PubMed K.M. Rau, Y.J. Chen, M.T. Sun, H.Y. Kang, Prognostic effects and regulation of activin A, maspin, and the androgen receptor in upper urinary tract urothelial carcinoma. Anticancer Res. 31, 1713–1720 (2011)PubMed
19.
go back to reference C. Tuygun, D. Kankaya, A. Imamoglu, A. Sertcelik, K. Zengin et al., Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol. Oncol. 29, 43–51 (2011)PubMedCrossRef C. Tuygun, D. Kankaya, A. Imamoglu, A. Sertcelik, K. Zengin et al., Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol. Oncol. 29, 43–51 (2011)PubMedCrossRef
20.
go back to reference S. Boorjian, S. Ugras, N.P. Mongan, L.J. Gudas, X. You et al., Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64, 383–388 (2004)PubMedCrossRef S. Boorjian, S. Ugras, N.P. Mongan, L.J. Gudas, X. You et al., Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64, 383–388 (2004)PubMedCrossRef
21.
go back to reference C. Mir, S.F. Shariat, T.H. van der Kwast, R. Ashfaq, Y. Lotan et al., Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study. BJU Int. 108, 24–30 (2011)PubMedCrossRef C. Mir, S.F. Shariat, T.H. van der Kwast, R. Ashfaq, Y. Lotan et al., Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study. BJU Int. 108, 24–30 (2011)PubMedCrossRef
22.
go back to reference S. Makela, L. Strauss, G. Kuiper, E. Valve, S. Salmi et al., Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract. Mol. Cell. Endocrinol. 170, 219–229 (2000)PubMedCrossRef S. Makela, L. Strauss, G. Kuiper, E. Valve, S. Salmi et al., Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract. Mol. Cell. Endocrinol. 170, 219–229 (2000)PubMedCrossRef
23.
go back to reference P. Buhler, P. Wolf, A. Katzenwadel, W. Schultze-Seemann, U. Wetterauer et al., Primary prostate cancer cultures are models for androgen-independent transit amplifying cells. Oncol. Rep. 23, 465–470 (2010)PubMed P. Buhler, P. Wolf, A. Katzenwadel, W. Schultze-Seemann, U. Wetterauer et al., Primary prostate cancer cultures are models for androgen-independent transit amplifying cells. Oncol. Rep. 23, 465–470 (2010)PubMed
24.
go back to reference H. Fridborg, E. Jonsson, P. Nygren, R. Larsson, Relationship between diagnosis-specific activity of cytotoxic drugs in fresh human tumour cells ex vivo and in the clinic. Eur. J. Cancer 35, 424–432 (1999)PubMedCrossRef H. Fridborg, E. Jonsson, P. Nygren, R. Larsson, Relationship between diagnosis-specific activity of cytotoxic drugs in fresh human tumour cells ex vivo and in the clinic. Eur. J. Cancer 35, 424–432 (1999)PubMedCrossRef
25.
go back to reference M.H. Yang, K.K. Chen, C.C. Yen, W.S. Wang, Y.H. Chang et al., Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology 59, 681–687 (2002)PubMedCrossRef M.H. Yang, K.K. Chen, C.C. Yen, W.S. Wang, Y.H. Chang et al., Unusually high incidence of upper urinary tract urothelial carcinoma in Taiwan. Urology 59, 681–687 (2002)PubMedCrossRef
26.
go back to reference C.C. Tzeng, H.S. Liu, C. Li, Y.T. Jin, R.M. Chen et al., Characterization of two urothelium cancer cell lines derived from a blackfoot disease endemic area in Taiwan. Anticancer Res. 16, 1797–1804 (1996)PubMed C.C. Tzeng, H.S. Liu, C. Li, Y.T. Jin, R.M. Chen et al., Characterization of two urothelium cancer cell lines derived from a blackfoot disease endemic area in Taiwan. Anticancer Res. 16, 1797–1804 (1996)PubMed
27.
go back to reference C.A. Reznikoff, L.J. Loretz, B.J. Christian, S.Q. Wu, L.F. Meisner, Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene. Carcinogenesis 9, 1427–1436 (1988)PubMedCrossRef C.A. Reznikoff, L.J. Loretz, B.J. Christian, S.Q. Wu, L.F. Meisner, Neoplastic transformation of SV40-immortalized human urinary tract epithelial cells by in vitro exposure to 3-methylcholanthrene. Carcinogenesis 9, 1427–1436 (1988)PubMedCrossRef
28.
go back to reference S.P. Ackland, M.J. Ratain, N.J. Vogelzang, K.E. Choi, M. Ruane et al., Pharmacokinetics and pharmacodynamics of long-term continuous-infusion doxorubicin. Clin. Pharmacol. Ther. 45, 340–347 (1989)PubMedCrossRef S.P. Ackland, M.J. Ratain, N.J. Vogelzang, K.E. Choi, M. Ruane et al., Pharmacokinetics and pharmacodynamics of long-term continuous-infusion doxorubicin. Clin. Pharmacol. Ther. 45, 340–347 (1989)PubMedCrossRef
29.
go back to reference E. Laor, Z.J. Schiffman, J.D. Braunstein, R.E. Reid, B.M. Tolia et al., Androgen receptors in bladder tumors. Urology 25, 161–163 (1985)PubMedCrossRef E. Laor, Z.J. Schiffman, J.D. Braunstein, R.E. Reid, B.M. Tolia et al., Androgen receptors in bladder tumors. Urology 25, 161–163 (1985)PubMedCrossRef
30.
go back to reference S.S. Shen, C.L. Smith, J.T. Hsieh, J. Yu, I.Y. Kim et al., Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 106, 2610–2616 (2006)PubMedCrossRef S.S. Shen, C.L. Smith, J.T. Hsieh, J. Yu, I.Y. Kim et al., Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 106, 2610–2616 (2006)PubMedCrossRef
31.
go back to reference H. Miyamoto, J.L. Yao, A. Chaux, Y. Zheng, I. Hsu et al., Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder. BJU Int. 109, 1716–1726 (2012)PubMedCrossRef H. Miyamoto, J.L. Yao, A. Chaux, Y. Zheng, I. Hsu et al., Expression of androgen and oestrogen receptors and its prognostic significance in urothelial neoplasm of the urinary bladder. BJU Int. 109, 1716–1726 (2012)PubMedCrossRef
32.
go back to reference K.S. Kang, I. Morita, A. Cruz, Y.J. Jeon, J.E. Trosko et al., Expression of estrogen receptors in a normal human breast epithelial cell type with luminal and stem cell characteristics and its neoplastically transformed cell lines. Carcinogenesis 18, 251–257 (1997)PubMedCrossRef K.S. Kang, I. Morita, A. Cruz, Y.J. Jeon, J.E. Trosko et al., Expression of estrogen receptors in a normal human breast epithelial cell type with luminal and stem cell characteristics and its neoplastically transformed cell lines. Carcinogenesis 18, 251–257 (1997)PubMedCrossRef
33.
go back to reference G.R. Cunha, W. Ricke, A. Thomson, P.C. Marker, G. Risbridger et al., Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development. J. Steroid Biochem. Mol. Biol. 92, 221–236 (2004)PubMedCrossRef G.R. Cunha, W. Ricke, A. Thomson, P.C. Marker, G. Risbridger et al., Hormonal, cellular, and molecular regulation of normal and neoplastic prostatic development. J. Steroid Biochem. Mol. Biol. 92, 221–236 (2004)PubMedCrossRef
34.
go back to reference R. Bhatia-Gaur, A.A. Donjacour, P.J. Sciavolino, M. Kim, N. Desai et al., Roles for Nkx3.1 in prostate development and cancer. Genes Dev. 13, 966–977 (1999)PubMedCrossRef R. Bhatia-Gaur, A.A. Donjacour, P.J. Sciavolino, M. Kim, N. Desai et al., Roles for Nkx3.1 in prostate development and cancer. Genes Dev. 13, 966–977 (1999)PubMedCrossRef
Metadata
Title
The expression and actions of androgen receptor in upper urinary tract urothelial carcinoma (UUTUC) tissues and the primary cultured cells
Authors
Chih-Rong Shyr
Chi-Cheng Chen
Teng-Fu Hsieh
Chao-Hsiang Chang
Wen-Lung Ma
Shuyuan Yeh
Edward Messing
Tsung-Heng Li
Fu-Yin Li
Chawnshang Chang
Publication date
01-02-2013
Publisher
Springer US
Published in
Endocrine / Issue 1/2013
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-012-9762-4

Other articles of this Issue 1/2013

Endocrine 1/2013 Go to the issue