Relation between Bcl-2, cell proliferation, and the androgen receptor status 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 progression to an androgen-insensitive disease. METHODS: Using double-labeling 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-grade prostatic intraepithelial neoplasia (HGPIN). RESULTS: In the peripheral and transition zone of the prostate gland, 77% of cycling (MIB-1 positive) epithelial cells coexpressed the Bcl-2 product and were phenotypically basal cells. Bcl-2 immunoreactive basal cells showed markedly reduced levels of the nuclear AR. In the central zone of the gland, increasing Bcl-2 immunoreactivity was detected in secretory luminal cell types that expressed the nuclear AR at low levels. 22% of HGPIN lesions (47 of 216 cases) overexpressed Bcl-2 in secretory luminal cell types, while most of HGPIN lesions (78%) showed the normal Bcl-2 phenotype restricted to the basal cell layer. No correlation was found between the Bcl-2 status and proliferative activity (P > 0.05). Conversely, markedly reduced levels of nuclear AR were detected in HGPIN overexpressing 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 the dysplastic epithelium.