Regulation of growth, PSA/PAP and androgen receptor expression by 1 alpha,25-dihydroxyvitamin D-3 in the androgen-dependent LNCaP cells

The involvement of vitamin D in prostate carcinogenesis was investigated using the human prostatic LNCaP cells. Incubation of the LNCaP with 100 nM 1 alpha,25-dihydroxyvitamin D-3 for 2 days resulted in a 30-40% suppression of cell growth, which was accompanied by a greater than 70% down-regulated expression of the proliferating cell nuclear antigen (PCNA). The intracellular and secreted forms of PSA showed a 2-fold increase following a 48 h culture in the presence of vitamin D-3. The vitamin D-3-elicited PSA increases were preceded by an induction of androgen receptor (AR) expression, as measured by Western blot analysis and by binding assays using [H-3]R1881 as the ligand. These results are consistent with the hypothesis that the growth inhibitory effects of vitamin D-3 is partially mediated through its ability to modulate PCNA expression. Moreover, vitamin D-3 may effect increases in PSA expression indirectly by up-regulating androgen receptors. (C) 1996 Academic Press, Inc.