| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Journal of Andrology, Vol 22, Issue 4 537-548, Copyright © 2001 by The American Society of Andrology
JOURNAL ARTICLE |
C. W. Gregory, R. T. Johnson Jr, S. C. Presnell, J. L. Mohler and F. S. French
Department of Pediatrics, University of North Carolina at Chapel, 27599, USA. cgregory@med.unc.edu
Human prostate cancer is initially dependent on androgens for growth, and androgen-dependent cells undergo apoptosis after castration. However, a subset of androgen-responsive cells survives and eventually proliferates in the absence of testicular androgen. The high levels of androgen receptor in both androgen-dependent and recurrent tumors led us to investigate androgen regulation of cell cycle proteins in human prostate cancer using the CWR22 xenograft. Cellular proliferation decreased dramatically in CWR22 tumors after castration. Testosterone propionate (TP) treatment of castrated mice restored cellular proliferation after 24-48 hours. Growth of CWR22 tumors in the absence of testicular androgen recurred several months after castration. CDK1 and CDK2, and cyclin A and cyclin B1 messenger RNAs were decreased 6 days after castration, increased 6-12 hours after TP treatment, and were expressed at high levels in recurrent CWR22 tumors. Coimmunoprecipitated cyclin B1/CDK1 and cyclin D1/CDK4 protein complexes decreased after castration and increased after TP treatment of castrated mice. In addition, CDK1 and CDK2 kinase activities were upregulated by androgen in parallel with hyperphosphorylation of retinoblastoma (Rb) protein. Despite the absence of testicular androgen in recurrent CWR22, the levels of these androgen-regulated cyclin/ CDK protein complexes and hyperphosphorylation of Rb were equal to or greater than in tumors from intact mice. The results indicate that androgen receptor regulates cellular proliferation by control of CDK and cyclins at the transcriptional level and by post-translational modifications that influence cell cycle protein activity.
This article has been cited by other articles:
 |
|
 |
|
  A. Seaton, P. Scullin, P. J. Maxwell, C. Wilson, J. Pettigrew, R. Gallagher, J. M. O'Sullivan, P. G. Johnston, and D. J. J. Waugh Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation Carcinogenesis, June 1, 2008; 29(6): 1148 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Periyasamy, M. Warrier, M. P. M. Tillekeratne, W. Shou, and E. R. Sanchez The Immunophilin Ligands Cyclosporin A and FK506 Suppress Prostate Cancer Cell Growth by Androgen Receptor-Dependent and -Independent Mechanisms Endocrinology, October 1, 2007; 148(10): 4716 - 4726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. I. Klokk, A. Kilander, Z. Xi, H. Waehre, B. Risberg, H. E. Danielsen, and F. Saatcioglu Kallikrein 4 Is a Proliferative Factor that Is Overexpressed in Prostate Cancer Cancer Res., June 1, 2007; 67(11): 5221 - 5230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Gomez, A. de las Pozas, T. Reiner, K. Burnstein, and C. Perez-Stable Increased expression of cyclin B1 sensitizes prostate cancer cells to apoptosis induced by chemotherapy Mol. Cancer Ther., May 1, 2007; 6(5): 1534 - 1543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, S.-Y. Chen, K. N. Ross, and S. P. Balk Androgens Induce Prostate Cancer Cell Proliferation through Mammalian Target of Rapamycin Activation and Post-transcriptional Increases in Cyclin D Proteins. Cancer Res., August 1, 2006; 66(15): 7783 - 7792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yuan, T. Li, H. Wang, T. Zhang, M. Barua, R. A. Borgesi, G. J. Bubley, M. L. Lu, and S. P. Balk Androgen Receptor Remains Critical for Cell-Cycle Progression in Androgen-Independent CWR22 Prostate Cancer Cells Am. J. Pathol., August 1, 2006; 169(2): 682 - 696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Gregory, Y. E. Whang, W. McCall, X. Fei, Y. Liu, L. A. Ponguta, F. S. French, E. M. Wilson, and H. S. Earp III Heregulin-Induced Activation of HER2 and HER3 Increases Androgen Receptor Transactivation and CWR-R1 Human Recurrent Prostate Cancer Cell Growth Clin. Cancer Res., March 1, 2005; 11(5): 1704 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Gregory, X. Fei, L. A. Ponguta, B. He, H. M. Bill, F. S. French, and E. M. Wilson Epidermal Growth Factor Increases Coactivation of the Androgen Receptor in Recurrent Prostate Cancer J. Biol. Chem., February 20, 2004; 279(8): 7119 - 7130. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Mohler, C. W. Gregory, O. H. Ford III, D. Kim, C. M. Weaver, P. Petrusz, E. M. Wilson, and F. S. French The Androgen Axis in Recurrent Prostate Cancer Clin. Cancer Res., January 15, 2004; 10(2): 440 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Martinez and M. Danielsen Loss of Androgen Receptor Transcriptional Activity at the G1/S Transition J. Biol. Chem., August 9, 2002; 277(33): 29719 - 29729. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
