COMMONALITY OF THE GENE PROGRAMS INDUCED BY EFFECTORS OF APOPTOSIS INANDROGEN-DEPENDENT AND ANDROGEN-INDEPENDENT PROSTATE CELLS

Prostate tissue is composed of both androgen-dependent and -independen t cells. To identify the gene program induced by effecters of apoptosi s in both of these cell types, we performed differential hybridization on a complementary DNA library prepared from an androgen-independent prostate cancer cell line, AT-3, exposed to ionomycin. Five distinct c omplementary DNAs representing ionomycin-inducible genes, designated p rostate apoptosis response (par) -1, -2, -3, -4, and -5, were identifi ed. Nucleotide sequencing identified par-1 as the rat homologue of a s erum- and oxidative stress-inducible gene, 3CH134/erp/CL100; par-2 as the injury-inducible gene HB-EGF encoding a heparin-binding epidermal growth factor-like growth factor; par-3 as the serum-inducible gene cy r-61; whereas par-4 and par-5 were novel, as judged by a GenBank searc h. par-1, -3, -4, and -5 were also induced in rat ventral prostate fol lowing castration, which causes androgen ablation, leading to apoptosi s of androgen-dependent prostate cells. Pretreatment of rats with nife dipine prior to castration abrogated inducible expression of the par g enes, indicating that their expression was downstream to Ca2+ elevatio n. Further characterization of these genes revealed that induction of par-4 is apoptosis specific: it is not induced by effecters of growth stimulation, oxidative stress and necrosis, or growth arrest in prosta te cells. Together, par-1, -3, -4, and -5 represent an apoptosis respo nse gene program common to both androgen-dependent and -independent pr ostate cells. Thus, cell death programs in prostate cells are comprise d of genes specifically