DIFFERENTIAL REGULATION OF MATRIX GLA PROTEIN (MGP) GENE-EXPRESSION BY RETINOIC ACID AND ESTROGEN IN HUMAN BREAST-CARCINOMA CELLS

Expression of matrix Gla protein (MGP) gene and its regulation by reti noic acid (RA) and estrogen was investigated in eight human breast can cer cell lines. The promoter region of the MGP gene contains a consens us retinoic acid response element (RARE) and the MGP gene expression h as been shown to be strongly induced by RA in other systems. Our resul ts suggest that RA negatively regulates MGP mRNA expression in human b reast cancer cells that have high levels of estrogen receptors (ER), i .e. MCF-7, ZR-75 and BT474 and positively regulates its expression m c ells with either no ERs, i.e. MDA-MB-468 or very low levels of ERs, i. e. T47D. This indicates that ER levels may affect RA modulation of MGP gene expression in human breast cancer cells. The inhibitory effect o f RA on MGP gene expression was abolished in RRO-I, the RA-resistant M CF-7 subline. We also demonstrate for the first time that estrogen str ongly induces MGP gene expression in ER-positive cells and that estrog en-mediated induction of MGP is blocked by RA even in otherwise RA-res istant cells.