Regulation of GCDFP-15 expression in human mammary cancer cells

Gross cystic disease fluid protein 15 (GCDFP-15) is a major protein compone nt of benign breast gross cysts. It is also found in approximately 50% of a ll breast cancer specimens. Androgen receptor (AR) mediated regulation of G CDFP-15 expression was investigated in the AR-positive human mammary cancer cell lines MFM-223 and ZR-75-1. Proliferation of MFM-223 and ZR-75-1 cells is inhibited by androgens. Ten nM 5 alpha-dihydrotestosterone stimulated t he expression of GCDFP-15 mRNA in MFM-223 (ca. 3-fold) and ZR-75-1 cancer c ells (ca. 30-fold) as well as the secretion of GCDFP-15 into the culture me dium. Competition experiments with DHT and the antiandrogens hydroxyflutami de and casodex confirmed the involvement of the AR in the regulation of GCD FP-15. Both antiandrogens inhibited GCDFP-15 mRNA expression even in the ab sence of DHT. AR mRNA was down-regulated in MFM-223 and ZR-75-1 cells (80 a nd 20% of the control, respectively) during incubation with DHT. Our data d emonstrate the effective inhibition of GCDFP-15 expression by pure antiandr ogens.