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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Chang, C. Lin, H. K. Yeh, S. Huang, K. E. Kang, H. Y. Hu, Y. C. |
| Description | Author Affiliation: Kang HY ( George Whipple Laboratory for Cancer Research, Department of Pathology, of Rochester Medical Center, Rochester, NY 14642, USA.); |
| Abstract | Although transforming growth factor-beta (TGF-beta) has been identified to mainly inhibit cell growth, the correlation of elevated TGF-beta with increasing serum prostate-specific antigen (PSA) levels in metastatic stages of prostate cancer has also been well documented. The molecular mechanism for these two contrasting effects of TGF-beta, however, remains unclear. Here we report that Smad3, a downstream mediator of the TGF-beta signaling pathway, functions as a coregulator to enhance androgen receptor (AR)-mediated transactivation. Compared with the wild-type AR, Smad3 acts as a strong coregulator in the presence of 1 nM 5alpha-dihydrotestosterone, 10 nM 17beta-estradiol, or 1 microM hydroxyflutamide for the LNCaP mutant AR (mtAR T877A), found in many prostate tumor patients. We further showed that endogenous PSA expression in LNCaP cells can be induced by 5alpha-dihydrotestosterone, and the addition of the Smad3 further induces PSA expression. Together, our findings establish Smad3 as an important coregulator for the androgen-signaling pathway and provide a possible explanation for the positive role of TGF-beta in androgen-promoted prostate cancer growth. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 98 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2001-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA-Binding Proteins Metabolism Receptors, Androgen Signal Transduction Physiology Trans-Activators Transcriptional Activation Transforming Growth Factor Beta Androgens Cell Line Gene Expression Prostate-Specific Antigen Genetics Prostatic Neoplasms Receptors, Calcitriol Receptors, Estrogen Receptors, Progesterone Recombinant Fusion Proteins Response Elements Smad3 Protein Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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