Characterization of a zinc-finger protein and its association with apoptosis in prostate cancer cells

Background: The transition from androgen-dependent to androgen-independent prostate cancer is not fully understood but appears to involve multiple gen etic changes. We have identified a gene, GC79, that is more highly expresse d in androgen-dependent LNCaP-FGC human prostate cancer cells than in andro gen-independent LNCaP-LNO human prostate cancer cells, Physiologic levels ( 0.1 nM) of androgens repress expression of GC79 messenger RNA (mRNA) in LNC aP-FGC cells. To determine the role of GC79, we cloned its complementary DN A (cDNA) and functionally characterized its product. Methods: The different ially expressed GC79 gene was cloned from human prostate cDNA libraries, se quenced, and transfected into mammalian cells to study its function. Expres sion of GC79 was analyzed in various adult and fetal human tissues and in p rostate glands of castrated rats. The association of GC79 expression and ap optosis was investigated in COS-1 and LNCaP cells transfected with GC79 cDN A, All statistical tests are two-sided. Results: Sequence analysis indicate s that GC79 encodes a large, complex, multitype zinc-finger protein, contai ning nine C2H2-type zinc-finger domains, a cysteine-rich region, and a GATA C-4-type zinc-finger domain. Castration-induced androgen withdrawal increa sed the expression of GC79 mRNA in the regressing rat ventral prostate, sug gesting that the expression of GC79 mRNA is associated with the process of apoptotic cell death in the rat ventral prostate. Transfection and inductio n of GC79 cDNA in both COS-1 and LNCaP prostate cancer cells led to an apop totic index that was eightfold higher (P<.001, two-sided Student's t test) than that observed in uninduced transfected cells. Conclusions: We have clo ned an androgen-repressible gene, GC79, that is potentially involved in apo ptosis, This finding may have implications for the development of androgen- independent prostate cancer and, ultimately, for the treatment of prostate cancer.