PubMed:10537131 JSONTXT 2 Projects

Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells. The goal of this study is to investigate the molecular mechanisms of androgen-independent growth in prostate cancer. We have established an androgen-independent prostatic carcinoma LNCaP-AI (defined as a LNCaP cell line that is capable of growing in charcoal-stripped serum) from the androgen-dependent LNCaP-FGC cells. In contrast to the androgen-independent PC-3 human prostate cancer cells, LNCaP-AI cells still express a similar level of androgen receptor as their parental cells and are sensitive to androgen stimulation. Compared with the parental LNCaP-FGC cells, LNCaP-AI cells are more resistant to apoptosis induced by 12-O-tetradecanoylphorbol-13-acetate and express a much higher level of antiapoptotic gene bcl-2 and cyclin-dependent kinase inhibitor p21, which may confer an enhanced antiapoptosis phenotype. On the other hand, expression of cyclin-dependent kinase inhibitor p16 is significantly reduced in the LNCaP-AI cells, implying the release of an inhibitory effect of p16 on cell cycle progression. Taken together, our results suggest that multiple factors contribute to the development of androgen-independent growth of prostatic carcinoma cells, including enhancement of cell antiapoptosis function, release of cell cycle inhibition, and stimulation of cell proliferation by alternative signaling pathways.