TY - JOUR T1 - Expression of Estrogen Sulfotransferase in MCF-7 Cells by cDNA Transfection Suppresses the Estrogen Response: Potential Role of the Enzyme in Regulating Estrogen-Dependent Growth of Breast Epithelial Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 555 LP - 560 VL - 286 IS - 1 AU - Yueming Qian AU - Chengjun Deng AU - Wen-Chao Song Y1 - 1998/07/01 UR - http://jpet.aspetjournals.org/content/286/1/555.abstract N2 - Estrogen sulfotransferase (EST) is a cytosolic enzyme that catalyzes the sulfonation of estrogens at the 3-hydroxyl position by use of 3′-phosphoadenosine-5′-phosphosulfate as an activated sulfate donor. Although largely known and studied as a phase II metabolic enzyme with prominent expression in the liver, the high substrate specificity of EST (with a highVmax/Km value for estrogen) suggests that expression of the enzyme in extrahepatic, estrogen target tissues, such as the breast epithelium, may constitute an effective mechanism for local estrogen regulation as well. In this study, we have evaluated the physiological significance of EST expression by cDNA transfection studies with use of the estrogen-dependent MCF-7 breast cancer cell line as a model system. We show that expression of EST in MCF-7 cells effectively reduces the cells’ response to physiological concentrations of estradiol (10 nM) by up to 70% as determined in an estrogen-responsive reporter gene assay. In addition, we demonstrate that expression of EST similarly inhibits estrogen-stimulated DNA synthesis and cell proliferation by 21% and 46%, respectively. (The thymidine incorporation rate was measured 3 days after and the cell numbers were counted 8 days after transfection.) These results provide direct evidence for the functional significance of in situ EST expression in the breast epithelium and suggest that abnormal regulation of the enzyme may have pathological implications in the development and maintenance of hormone-dependent breast carcinomas. The American Society for Pharmacology and Experimental Therapeutics ER -