RELATION BETWEEN BCL-2, CELL-PROLIFERATION, AND THE ANDROGEN RECEPTORSTATUS IN PROSTATE TISSUE AND PRECURSORS OF PROSTATE-CANCER

BACKGROUND. Several recent studies have suggested an important role of the apoptosis suppressing Bcl-2 gene product in prostate cancer progr ession to an androgen-insensitive disease. METHODS. Using double-label ing techniques, we have investigated the nuclear androgen receptor (AR ) status and the proliferation-associated MIB-1 antigen immunoprofile of Bcl-2 expressing cell types in benign prostate tissue, and high-gra de prostatic intraepithelial neoplasia (HGPIN). RESULTS. In the periph eral and transition zone of the prostate gland, 77% of cycling (MIB-1 positive) epithelial cells coexpressed the Bcl-2 product and were phen otypically basal cells. Bcl-2 immunoreactive basal cells showed marked ly reduced levels of the nuclear AR. In the central zone of the gland, increasing Bcl-2 immunoreactivity was detected in secretory luminal c ell types that expressed the nuclear AR at low levels. 22% of HGPIN le sions (47 of 216 cases) overexpressed Bcl-2 in secretory luminal cell types, while most of HGPIN lesions (78%) showed the normal Bcl-2 pheno type restricted to the basal cell layer. No correlation was found betw een the Bcl-2 status and proliferative activity (P > 0.05). Conversely , markedly reduced levels of nuclear AR were detected in HGPIN overexp ressing the Bcl-2 gene product. CONCLUSIONS. The present data suggest that Bcl-2 prevents the proliferation compartment from apoptotic cell death. The aberrant expression of the Bcl-2 gene product in subsets of HGPIN is associated with decreasing levels of the nuclear AR and may confer resistance to the androgen-dependent apoptotic cell death in th e dysplastic epithelium. (C) 1998 Wiley-Liss, Inc.