REGULATION OF RAT DOC-2 GENE DURING CASTRATION-INDUCED RAT VENTRAL PROSTATE DEGENERATION AND ITS GROWTH-INHIBITORY FUNCTION IN HUMAN PROSTATIC-CARCINOMA CELLS

Androgen is a mitogen as well as a morphogen for prostatic epithelium. However, the detailed mechanisms of these distinct androgenic actions have not yet been delineated. Therefore, we employed differential dis play PCR to unveil any potential genes that may be involved in these p rocesses. In this study, we report the isolation and characterization of two alternative splicing forms (p82 and p59) of C9 complementary DN A, the rat homolog of the human deletion of ovarian carcinoma 2 (DOC-2 ) gene and mouse p96 phosphoprotein, from rat ventral prostate (VP). W e found that C9 was up-regulated in rat VP after castration, suggestin g that C9 may be regulated by androgen receptor directly or indirectly during prostate degeneration. A similar regulatory pattern was also o bserved in both the seminal vesicle and dorsolateral prostate, but not in the coagulating gland or other androgen-independent organs. Immuno histochemical analysis of rat VP demonstrated that C9 is detected in t he basal epithelia and surrounding stromal cells after prolonged castr ation. Ribonuclease protection assay and Western blot analysis reveale d that p59 is the predominant C9 isoform in rat VP. To unveil the func tion of C9 in cell growth, we transfected p59 complementary DNA into t he C4-2 cells, a derivative of the LNCaP prostatic carcinoma cell Line . The p59 stable transfectants exhibited a slower growth rate and an i ncrease in the cell fraction in the G(1) phase under our experimental conditions. These data indicate that C9-p59 has growth inhibitory acti vity for prostatic epithelial cells. Taken together, our results sugge st that C9 is upregulated during prostate degeneration process and may play an active role in the proliferation and differentiation of prost atic epithelium.