HOXC Family Gene Expression in Prostate Cancer: A Mechanism Contribution to Androgen Independence

摘要

This application proposed that HOXC gene overexpression would inhibit androgen-mediated gene expression. More speculatively, it proposed further that this inhibition may predispose prostate cancer cells to become partially androgen-independent for growth even before the imposition of androgen ablation therapy. A series of experiments in cell culture models and in cell-free transcription were proposed to address these two hypotheses. Experimental data described below support the contention that androgen-mediated transcription is inhibited by HOX overexpression. Curiously, the activity of the vitamin D receptor, another nuclear receptor that plays a key role in the control of prostate cancer growth, can be either inhibited or potentiated by HOXC overexpresslon. The data suggest that the role of HOXC overexpression on prostate cancer may be a complex one. Addressing the second hypothesis that HOXC overexpression could affect the development of androgen-independence is experimentally tricky to design in a way to adequately and appropriately test the hypothesis. To lay the groundwork for such experiments a more thorough characterization of the effects of androgens on prostate cancer lines, especially LNCaP has led to and expanded examination of the mechanisms underlying the biphasic actions of androgens on prostate cells and the complex interplay of the controls governing cell cycle and apoptosis. Specific experimental findings are described in the following section.