Title: Estrogen receptor alpha and Sp1 regulate progesterone receptor gene expression.

Authors: Schultz, Jennifer R; Petz, Larry N; Nardulli, Ann M

Published In Mol Cell Endocrinol, (2003 Mar 28)

Abstract: The progesterone receptor (PR) gene is induced by estrogen in reproductive and mammary tissues and in MCF-7 human breast cancer cells even though the human PR gene lacks an estrogen response element. We have identified a region from -80 to -34 in the PR gene that contains two Sp1 sites and confers estrogen responsiveness to a heterologous promoter in an estrogen and estrogen receptoralpha (ERalpha)-dependent manner. Sp1 present in MCF-7 nuclear extracts and purified Sp1 bind to and protect both Sp1 sites from DNase I cleavage, but the proximal Sp1 site is preferentially protected. Mutation of either Sp1 site decreases Sp1-DNA complex formation and ERalpha-mediated transactivation. ERalpha enhances Sp1 binding, but does not interact directly with the -80/-34 region. Our studies suggest that ERalpha confers estrogen responsiveness to the PR gene by enhancing Sp1 interaction with the Sp1 site in the -80/-34 region of the human PR gene.

PubMed ID: 12706304

MeSH Terms: Binding Sites; Breast Neoplasms/genetics*; Breast Neoplasms/metabolism; DNA Footprinting; Estrogen Receptor alpha; Estrogens/metabolism; Gene Expression Regulation*; Genes, Reporter; Humans; Mutation; Promoter Regions, Genetic; Receptors, Estrogen/physiology*; Receptors, Progesterone/genetics*; Receptors, Progesterone/metabolism; Receptors, Thyroid Hormone/genetics; Receptors, Thyroid Hormone/metabolism; Response Elements/physiology*; Sp1 Transcription Factor/physiology*; Transfection; Tumor Cells, Cultured