ANDROGEN RECEPTOR-ETS PROTEIN-INTERACTION IS A NOVEL MECHANISM FOR STEROID HORMONE-MEDIATED DOWN-MODULATION OF MATRIX METALLOPROTEINASE EXPRESSION

Matrix metalloproteinases belong to a family of structurally related e nzymes that plays important role in tissue morphogenesis, differentiat ion, and wound healing. Their expression is negatively regulated by se veral members of the steroid hormone receptor family. This is thought to occur through interaction of the steroid receptors with the transcr iption factor AP-1 that is otherwise required for positive regulation. Here, we demonstrate that AP-1 is not always a target for downregulat ion of expression of matrix metalloproteinases by steroid receptors, A ndrogen receptor negatively regulates matrix metalloproteinase-1 expre ssion not through AP-1 but through a family of Ets-related transcripti on factors that are also required for positive regulation. This negati ve regulation is specific for the androgen receptor. It does not requi re the DNA binding activity but needs amino terminal sequences of the receptor. These results identify a novel regulatory pathway for negati ve regulation utilized by a member of the steroid hormone receptor fam ily for down-regulating the expression of matrix metalloproteinases.