Induction of Androgen Receptor-Dependent Apoptosis in Prostate Cancer Cells by the Retinoblastoma Protein

Xintao Wang, Haiyun Deng, Indranil Basu, Liang Zhu

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Re-expression of a tumor suppressor in tumor cells that lack it is an effective way to study its functional activities. However, because tumor cells contain multiple mutations, tumor suppressor functions that are dependent on (an)other regulators are unlikely to be identified by its re-expression alone if the other regulators are also mutated. In this study, we show that re-expression of retinoblastoma (RB) together with the androgen receptor (AR) in RB- and AR-deficient prostate cancer DU-145 cells resulted in an apoptotic activity, acting through the mitochondria damage-initiated caspase activation pathway, which was not present when RB, or the AR, was re-expressed alone. The ability of RB + AR to induce mitochondria damage was dependent on the proapoptotic proteins Bax and Bak and could be blocked by the antiapoptotic protein Bcl-xL. Coexpressed AR did not detectably change RB's regulation of E2F and cell cycle progression in culture. On the other hand, coexpressed RB could activate the transactivation activity of the AR in an androgen-depleted media. Although androgen induced greater AR transactivation activity in this condition, it did not induce apoptosis in the absence of coexpressed RB. Analysis of mutants of RB and the AR indicated that intact pocket function of RB and the transactivation activity of the AR were required for RB + AR-induced apoptosis. These results provide direct functional data for an AR-dependent apoptosis-inducing activity of RB and highlight the importance of cell type-specific regulators in obtaining a more complete understanding of RB.

Original languageEnglish (US)
Pages (from-to)1377-1385
Number of pages9
JournalCancer research
Volume64
Issue number4
DOIs
StatePublished - Feb 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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