REEXPRESSION OF ELAFIN IN 21MT2 BREAST CARCINOMAS BY PHORBOL 12-MYRISTATE 13-ACETATE IS MEDIATED BY THE AP1 SITE IN THE ELAFIN PROMOTER

elafin is a unique elastase inhibitor. It is differentially expressed at the transcriptional level in human normal mammary epithelial cells and carcinomas. The elafin gene is induced by PIMA in 21MT2 breast tum or cells. By deletion analysis and mutagenesis, we have identified the Ap1 site in the promoter as the cis element mediating transcriptional activation of elafin in 70N normal breast cells and its induction by phorbol 12-myristate 13-acetate (PMA) in 21MT2 breast tumors. PIMA tre atment induces AP1 factor expression, which binds to the Ap1 site of t he elafin promoter, Mutation of this Ap1 abolishes the capability of i nduction by PMA. Furthermore, our data provide a basis for therapeutic manipulation of proteinase inhibitors such as elafin.