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Cloning and Characterization of a Novel Gene That Is Regulated by Estrogen and Is Associated with Mammary Gland Carcinogenesis¹

Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Departments of Medicine (D.M., L.E.C., M.A.A.-J., H.T.H.), Pharmacology and Therapeutics (M.A.A.-J.), and Pathology and Oncology (L.A.), McGill University, Montréal, Québec, Canada H3T 1E2

Address all correspondence and requests for reprints to: Lorraine E. Chalifour, Ph.D., Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Department of Medicine, McGill University, 3755 Chemin Côte Ste Catherine, Montréal, Québec, Canada H3T 1E2. E-mail: lorraine.chalifour{at}mcgill.ca Or Hung The Huynh at his current

Estrogens play a role in mammary gland function and are implicated in mammary carcinogenesis. We report the cloning of a novel gene [steroid-sensitive gene 1 (SSG1)] that is regulated by E₂ 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 normal mammary tissue and to endothelial cells of 7,12-dimethylbenz(a)antracene-induced mammary tumors. Treatment of rats with E₂ at 1.2 or 2.4 µg/kg·day for 21 days increases SSG1 protein levels in mammary tissue by 16-fold compared with controls. Removal of E₂ after a 14-day treatment decreases SSG1 protein levels 6-fold and 3-fold at 120 and 144 h, respectively. Treatment 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 greater than SSG1 levels in resting mammary tissue, and 8-fold higher than protein levels expressed in lactating mammary glands. We propose that SSG1 plays a role in estrogen functions, and its overexpression is correlated with mammary carcinogenesis.

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