Relation between Bcl-2, cell proliferation, and the androgen receptor status in prostate tissue and precursors of prostate cancer

✍ Scribed by Bonkhoff, Helmut; Fixemer, Thomas; Remberger, Klaus

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 401 KB
• Volume: 34
• Category: Article
• ISSN: 0270-4137
• DOI: 10.1002/(sici)1097-0045(19980301)34:4<251::aid-pros2>3.0.co;2-k

✦ Synopsis

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.