Androgens down-regulate bcl-2 protooncogene expression in ZR-75-1 human breast cancer cells

Although a large proportion of primary human breast cancers express the androgen receptor, and treatment with androgens exerts beneficial effects in women with breast cancer, the role and especially the mechanism of action of androgens in breast cancer development and growth are not well understood. The potential effect of androgens on bcl-2 protooncogene expression was investigated in a human breast cancer cell line whose proliferation is known to be inhibited by androgens. The estrogen-responsive ZR-75-1 cells were grown in the presence or absence of 5 alpha-dihydrotestosterone (DHT), alone or in combination with 17 beta-estradiol. DHT caused a marked down-regulation of Bcl-2 protein and messenger RNA levels in both the presence and absence of 17 beta-estradiol. The inhibitory effect of DHT was completely prevented by coincubation with the pure antiandrogen hydroxyflutamide. The present data indicate that androgens can downregulate bcl-2 protooncogene levels via an androgen receptor-mediated mechanism, thus providing a novel mechanism for their known inhibitory effect on breast cancer cell growth.