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TGF-beta signaling and androgen receptor status determine apoptotic cross-talk in human prostate cancer cells

Meng-Lei Zhu1, James V Partin, Elizabeth M Bruckheimer

  • 1Division of Urology, Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.

The Prostate
|January 1, 2008
PubMed
Abstract

Insights

Androgen receptor (AR) status dictates prostate cancer cell sensitivity to transforming growth factor-beta 1 (TGF-beta1) induced apoptosis. This interaction influences the development of androgen-independent prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Transforming growth factor-beta (TGF-beta) and androgens synergistically promote apoptosis in prostate cancer cells.
  • The role of the androgen receptor (AR) in this combined effect requires further investigation.

Purpose of the Study:

  • To investigate the contribution of AR in the combined effects of TGF-beta and dihydrotestosterone (DHT) on apoptosis regulation.
  • To analyze AR- and TGF-beta-mediated transcriptional activity in prostate cancer cells.

Main Methods:

  • Transient transfections and luciferase assays were used to evaluate transcriptional activation in response to TGF-beta and DHT.
  • AR cellular distribution and interaction with Smad4 were assessed in relation to apoptotic response.

Main Results:

  • TGF-beta signaling induced AR-mediated transcriptional activation on androgen-responsive promoters (probasin, PSA).
  • DHT enhanced TGF-beta1-induced transcriptional activity via AR-Smad4 interaction in LNCaP-TbetaRII and PC-3-AR cells.
  • DHT did not enhance TGF-beta-mediated apoptosis in PC-3 AR (wt) cells, indicating AR status is crucial.

Conclusions:

  • AR status determines prostate cancer cell sensitivity to TGF-beta1-induced apoptosis.
  • TGF-beta and AR pathways converge, impacting androgen-independent prostate cancer development.
  • AR status is significant in understanding the emergence of androgen-independent prostate tumors.

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