| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Oncology Research [S. Y., G. B. M., F. X., A. K.], The Divisions of Urology [S. Y., J. T.], Reproductive Science [T. J. B.], and Hematology-Oncology [A. K.], and Departments of Surgery [J. T.], Obstetrics and Gynecology [G. B. M., T. T. B.], and Medicine [A. K.], The Toronto Hospital and University of Toronto, Toronto, Ontario M5G 1L7, Canada
A full length human androgen receptor complementary DNA was introduced into androgen receptor-negative PC-3 cells to determine if androgen sensitivity could be established in this cell line and to assess what influence, if any, androgen exposure would have on the growth of these cells. The androgen receptor complementary DNA was inserted into pSG5 in the region controlled by the SV40 promoter. This construct was cotransfected with pSR1neo into PC-3 cells and stably transfected cells were selected and screened for the expression of the androgen receptor. Active expression of the receptor was demonstrated by Western blotting using a rabbit anti-androgen receptor antiserum and by [3H]methyltrienolone binding to cytosol extracts. Saturation ligand-binding analysis revealed the presence of a single class, high affinity (Kd = 0.122 nM) androgen-binding site in cytosol extracts of transfected cells but not in extracts from mock-transfected cells. In cells expressing the transfected androgen receptor, androgen decreased the proliferation rate and cloning efficiency and induced a more differentiated phenotype. These results demonstrate that PC-3 cells have retained the mechanisms required to respond to the activated androgen receptor and that the loss of androgen sensitivity in these cells is due to the lack of functional androgen receptor. This also provides a technique for determining whether androgen-resistant tumor cells contain functional androgen receptors or whether androgen sensitivity is due to abnormalities in downstream signaling pathways. The apparent androgen-induced decreased malignant state of these transfected cells suggests new directions for the treatment of prostate cancer.
1 Portions of this study were presented at the Annual Convention of the American Urological Association held May 10–14, 1992, in Washington, D.C. This work was supported by an operating grant from University-Industry Initiatives Fund of the Province of Ontario.
2 Present address: Cleveland Clinic Foundation, Department of Cancer Biology, NN1, 9500 Euclid Ave., Cleveland, OH 94195.
3 To whom requests for reprints should be addressed, at The Toronto Hospital, General Division, EN-14-209, 200 Elizabeth St., Toronto, Ontario M5G 2C4, Canada.
4 Canadian MRC and McLaughlin Scientist.
6 Senior Cancer Research Scientist of the National Cancer Institute of Canada.
Received 7/17/92. Accepted 1/11/93.
This article has been cited by other articles:
|
|
 |
|
  X. Wang, Y. Li, X. Zhu, Y. Wang, F. Diao, and J. Lu Signal regulatory protein {alpha}1 is involved in the inhibitory effect of glucocorticoid receptor on the proliferation of murine macrophage RAW264.7 cell and mouse peritoneal macrophage J. Mol. Endocrinol., November 1, 2008; 41(5): 393 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. D. Martinez, R. J. Jasavala, I. Hinkson, L. D. Fitzgerald, J. S. Trimmer, H.-J. Kung, and M. E. Wright RNA Editing of Androgen Receptor Gene Transcripts in Prostate Cancer Cells J. Biol. Chem., October 31, 2008; 283(44): 29938 - 29949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Niu, S. Altuwaijri, K.-P. Lai, C.-T. Wu, W. A. Ricke, E. M. Messing, J. Yao, S. Yeh, and C. Chang Androgen receptor is a tumor suppressor and proliferator in prostate cancer PNAS, August 26, 2008; 105(34): 12182 - 12187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Peng, F. Chen, J. Melamed, L. Chiriboga, J. Wei, X. Kong, M. Mcleod, Y. Li, C. X. Li, A. Feng, et al. Distinct nuclear and cytoplasmic functions of androgen receptor cofactor p44 and association with androgen-independent prostate cancer PNAS, April 1, 2008; 105(13): 5236 - 5241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Peng, C. X. Li, F. Chen, Z. Wang, M. Ligr, J. Melamed, J. Wei, W. Gerald, M. Pagano, M. J. Garabedian, et al. Stimulation of Prostate Cancer Cellular Proliferation and Invasion by the Androgen Receptor Co-Activator ARA70 Am. J. Pathol., January 1, 2008; 172(1): 225 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhou, H. Wu, P. Lee, and Z. Wang Roles of the androgen receptor cofactor p44 in the growth of prostate epithelial cells. J. Mol. Endocrinol., October 1, 2006; 37(2): 283 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zheng, C. Cai, J. Omwancha, S.-Y. Chen, T. Baslan, and L. Shemshedini SUMO-3 Enhances Androgen Receptor Transcriptional Activity through a Sumoylation-independent Mechanism in Prostate Cancer Cells J. Biol. Chem., February 17, 2006; 281(7): 4002 - 4012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-L. Hsu, Y.-L. Chen, H.-J. Ting, W.-J. Lin, Z. Yang, Y. Zhang, L. Wang, C.-T. Wu, H.-C. Chang, S. Yeh, et al. Androgen Receptor (AR) NH2- and COOH-Terminal Interactions Result in the Differential Influences on the AR-Mediated Transactivation and Cell Growth Mol. Endocrinol., February 1, 2005; 19(2): 350 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fu, M. Rao, C. Wang, T. Sakamaki, J. Wang, D. Di Vizio, X. Zhang, C. Albanese, S. Balk, C. Chang, et al. Acetylation of Androgen Receptor Enhances Coactivator Binding and Promotes Prostate Cancer Cell Growth Mol. Cell. Biol., December 1, 2003; 23(23): 8563 - 8575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Nishimura, H.-J. Ting, Y. Harada, T. Tokizane, N. Nonomura, H.-Y. Kang, H.-C. Chang, S. Yeh, H. Miyamoto, M. Shin, et al. Modulation of Androgen Receptor Transactivation by Gelsolin: A Newly Identified Androgen Receptor Coregulator Cancer Res., August 15, 2003; 63(16): 4888 - 4894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Pizzi, J. Gladu, L. Carpio, D. Miao, D. Goltzman, and S. A. Rabbani Androgen Regulation of Parathyroid Hormone-Related Peptide Production in Human Prostate Cancer Cells Endocrinology, March 1, 2003; 144(3): 858 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Whitacre, S. Chauhan, T. Davis, D. Gordon, A. E. Cress, and R. L. Miesfeld Androgen Induction of in Vitro Prostate Cell Differentiation Cell Growth Differ., January 1, 2002; 13(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Soto and C. Sonnenschein The Two Faces of Janus: Sex Steroids as Mediators of Both Cell Proliferation and Cell Death J Natl Cancer Inst, November 21, 2001; 93(22): 1673 - 1675. [Full Text] [PDF]
|
|
|
|
|
|
H.-K. Lin, S. Yeh, H.-Y. Kang, and C. Chang Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor PNAS, June 7, 2001; (2001) 121173298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Bonaccorsi, V. Carloni, M. Muratori, A. Salvadori, A. Giannini, M. Carini, M. Serio, G. Forti, and E. Baldi Androgen Receptor Expression in Prostate Carcinoma Cells Suppresses {alpha}6{beta}4 Integrin-Mediated Invasive Phenotype Endocrinology, September 1, 2000; 141(9): 3172 - 3182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Y. Zhao, D. M. Peehl, N. M. Navone, and D. Feldman 1{alpha},25-Dihydroxyvitamin D3 Inhibits Prostate Cancer Cell Growth by Androgen-Dependent and Androgen-Independent Mechanisms Endocrinology, July 1, 2000; 141(7): 2548 - 2556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Shen, M. Sumitomo, J. Dai, A. Harris, D. Kaminetzky, M. Gao, K. L. Burnstein, and D. M. Nanus Androgen-Induced Growth Inhibition of Androgen Receptor Expressing Androgen-Independent Prostate Cancer Cells Is Mediated by Increased Levels of Neutral Endopeptidase Endocrinology, May 1, 2000; 141(5): 1699 - 1704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Schrader and G. M. Cooke Examination of Selected Food Additives and Organochlorine Food Contaminants for Androgenic Activity in Vitro Toxicol. Sci., February 1, 2000; 53(2): 278 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Xing and S. A. Rabbani Regulation of Urokinase Production by Androgens in Human Prostate Cancer Cells: Effect on Tumor Growth and Metastases in Vivo Endocrinology, September 1, 1999; 140(9): 4056 - 4064. [Abstract] [Full Text]
|
|
|
|
|
|
R. T. Prehn On the Prevention and Therapy of Prostate Cancer by Androgen Administration Cancer Res., September 1, 1999; 59(17): 4161 - 4164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-F. Lin, T.-C. Meng, P. S. Rao, C. Chang, A. H. Schonthal, and F.-F. Lin Expression of Human Prostatic Acid Phosphatase Correlates with Androgen-stimulated Cell Proliferation in Prostate Cancer Cell Lines J. Biol. Chem., March 6, 1998; 273(10): 5939 - 5947. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Szelei, J. Jimenez, A. M. Soto, M. F. Luizzi, and C. Sonnenschein Androgen-Induced Inhibition of Proliferation in Human Breast Cancer MCF7 Cells Transfected with Androgen Receptor Endocrinology, April 1, 1997; 138(4): 1406 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. V. Nazareth and N. L. Weigel Activation of the Human Androgen Receptor through a Protein Kinase A Signaling Pathway J. Biol. Chem., August 16, 1996; 271(33): 19900 - 19907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Ting, S. Yeh, K. Nishimura, and C. Chang Supervillin associates with androgen receptor and modulates its transcriptional activity PNAS, January 22, 2002; 99(2): 661 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-K. Lin, S. Yeh, H.-Y. Kang, and C. Chang Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor PNAS, June 19, 2001; 98(13): 7200 - 7205. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
