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Papers In Press, published online ahead of print June 29, 2000
Department of Oncology, Johns Hopkins University, Baltimore, MD 21231
Corresponding Author: saras{at}welchlink.welch.jhu.edu
The majority of breast carcinomas show reduced or no expression of the transcription factor, HOXA5. Recently, we have shown that HOXA5 is a potent transactivator of p53 in breast cells and thus may affect the response of breast cancer cells to DNA damage. To determine whether HOXA5 played a role in growth and homeostasis in breast cells, we studied its interaction with the progesterone receptor. The progesterone receptor (PR) belongs to the superfamily of nuclear receptors whose members co-ordinate morphogenesis of the mammary gland in response to binding to their cognate ligands. An increased expression of the endogenous PR gene was seen in MCF-7 cells following induced expression of an exogenously transfected HOXA5 gene. HOXA5, but not HOXB4, ÐB5 or ÐB7 activated the PR promoter in two breast cancer cell lines, MCF-7 and Hs578T. Deletion and mutation analysis of the promoter identified a single HOXA5-binding site required for transactivation of the PR gene by HOXA5. HOXA5 binds directly to this site in the PR promoter. Thus, HOXA5 may behave as a transcriptional regulator of multiple target genes, two among which are p53 and the progesterone receptor.
J. Biol. Chem, 10.1074/jbc.C000324200
Submitted on May 15, 2000
Revised on June 27, 2000
Accepted on June 29, 2000
HOXA5 regulates expression of the progesterone receptor
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