Cloning and characterization of a novel gene that is regulated by estrogenand is associated with mammary gland carcinogenesis

Estrogens play a role in mammary gland function and are implicated in mamma ry carcinogenesis. We report the cloning of a novel gene [steroid-sensitive gene 1 (SSG1)] that is regulated by E, in the rat uterus and mammary gland . The full-length SSG1 complementary DNA has an open reading frame of 1158 nucleotides encoding a putative protein of 385 amino acids. A SSG1-specific antibody recognizes a 40-kDa protein localized to myoepithelial cells of n ormal mammary tissue and to endothelial cells of 7,12-dimethylbenz(a)antrac ene-induced mammary tumors. Treatment of rats with E-2 at 1.2 or 2.4 mug/kg .day for 21 days increases SSG1 protein levels in mammary tissue by 16-fold compared with controls. Removal of E-2 after a 14-day treatment decreases SSG1 protein levels 6-fold and 3-fold at 120 and 144 h, respectively. Treat ment of rats with the estrogen antagonists tamoxifen or ICI 182,780 did not affect SSG1 protein levels compared with controls. SSG1 protein levels in 7,12-dimethylbenz(a)antracene-induced rat mammary tumors were 23-fold great er than SSG1 levels in resting mammary tissue, and 8-fold higher than prote in levels expressed in lactating mammary glands. We propose that SSG1 plays a role in estrogen functions, and its overexpression is correlated with ma mmary carcinogenesis.