P16 Axis in Androgen-Dependent Proliferation of Prostate Cancer Cells
Annual rept. 1 Apr 2002-31 Mar 2003
ALBERT EINSTEIN COLL OF MEDICINE OF (YESHIVA UNIV) BRONX NY
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The purpose of this study is to understand the role of the pl6 growth control axis in androgen dependent proliferation of prostate cancer cells. The pl6 axis contains two tumor suppressors pl6lnk4a and RB, cyclin D-dependent kinases, and transcription factor E2F. We hypothesized that functions of the pl6 axis can influence androgen-dependence of prostate cancer cells. To test this hypothesis, we proposed to use controlled expression techniques to determine whether disruption of pl6 axis function can lead to androgen independence in human androgen-dependent prostate cancer cells LNCaP and, on the other hand, whether restoration of pl6 axis function can restore androgen-dependence in androgen-independent prostate cancer cells DU-l45 . We have now established LNCaP derivative cell lines that can provide inducible expression of exogenously introduced proteins. In DU-l45 cells, we have discovered that restoration of protein expression of pRB and the androgen receptor cause cell death. This finding reveals a novel functional relationship between RB and the AR in prostate cancer biology and may provide potential strategy for prostate cancer gene therapy.
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