Interactions Between Cell Cycle Control Proteins and the Androgen Receptor in Prostate Cancer
Annual rept. 4 Feb 2003-3 Feb 2004
COLUMBIA UNIV NEW YORK
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Studies carried out during the past year have confirmed and extended our novel discovery that the cell cycle control protein cyclin dependent kinase 6 CDK6 can bind to the androgen receptor AR and markedly stimulate its transcriptional activity in human prostate cancer cells. Furthermore, this effect does not require the kinase activity of CDK6. In studies with variants of the AR we found that short CAG repeats in exon 1 of the AR, which occur more frequently in African American AR men with prostate cancer, were more responsive to the stimulatory effects of CDK6 than an AR with long CAG repeats. In addition, a point mutated AR T877A, known to frequently occur in human prostate cancer, displayed dramatic stimulation by CDK6 in cells treated with dihydrotestosterone DHT, b- estradiol or progesterone. Taken together, these results suggest that CDK6 may play an important role in enhancing the development and progression of prostate cancer. It may therefore provide a prognostic marker and potential target for the prevention and therapy of prostate cancer.
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