Estrogen induction of the cyclin D1 promoter: involvement of a cAMP response-like element.

摘要: Estrogens induce cell proliferation in target tissues by stimulating progression through the G1 phase of cycle. Induction cyclin D1 expression is a critical feature mitogenic action estrogen. We have determined region between −96 and −29 promoter that confers regulation estrogens human mammary carcinoma cells MCF-7. This encompasses unique known transcription factor binding site with sequence potential cAMP response element (CRE-D1). The induction strictly hormone dependent requires DNA domain as well both AF-1 AF-2 domains estrogen receptor (ER) α. Destruction CRE-D1 motif caused complete loss responsiveness. Both c-Jun ATF-2 transactivated transient transfection experiments, clear additional increase was detected when ER cotransfected either or but not alone. Furthermore, dominant negative variant c-Jun, TAM67, completely abolished absence presence ER. show homodimers ATF-2/c-Jun heterodimers, homodimers, were able to bind CRE promoter. To interpret these results, we propose mechanism which heterodimers mediate activation represents pathway control cells.