Dihydrotestosterone Enhances Transforming Growth Factor- -Induced Apoptosis in Hormone-Sensitive Prostate Cancer Cells

Publisher Website
Google Scholar
Abstract
In this study, the potential interactions between dihydrotestos- terone (DHT), a survival factor, and transforming growth factor-b (TGF-b), an apoptotic inducer, were examined in a derivative of the hormone-sensitive prostate cancer cell line LNCaP. The LNCaP TGF-b receptor II cells, engineered to express TGF-b receptor II, are sensitive to both DHT and TGF-b. Surprisingly, when the LNCaP TGF-b receptor II cells were treated with TGF-b in the presence of physiological levels of DHT, both cell cycle arrest and apoptosis in- duction were significantly enhanced over TGF-b alone. This effect temporally correlated with an increased expression of the cell cycle regulator p21 as well as the apoptotic executioner, procaspase-1, and a parallel down-regulation of the antiapoptotic protein, bcl-2. Expres- sion of bax and caspase-3 proteins remained unchanged following treatment. Furthermore, apoptosis induction was suppressed by the caspase-1 inhibitor, z-YVAD, but not the caspase-3 inhibitor, z-DQMD, thus demonstrating the functional significance of increased procaspase-1 expression in TGF-b-mediated apoptosis in prostate cancer cells. These results indicate that TGF-b-mediated apoptosis can actually be enhanced by androgens through specific mechanisms involving cell cycle and apoptosis regulators and provide initial evi- dence on the ability of physiological levels of androgens to stimulate the intrinsic apoptotic potential of prostate cancer cells. Therefore, this study provides a molecular basis for the priming of prostate cancer cells for maximal apoptosis induction, during hormone- ablation therapy. (Endocrinology 142: 2419 -2426, 2001)

This publication has 0 references indexed in Scilit: