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Submitted on June 1, 2003
Accepted on October 27, 2003
1 Department of Chemical Engineering and Applied Chemistry, University of Toronto, Banting and Best Department of Medical Research, University of Toronto, Department of Physical and Environmental Sciences, University of Toronto at Scarborough, Department of Chemistry, Biology and Chemical Engineering, Ryerson University, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: edwards{at}chem-eng.utoronto.ca.
Estrogen receptors are nuclear transcription factors that regulate gene expression in response to estrogen and estrogen-like compounds. Identification of estrogen-regulated genes in target cells is an essential step toward understanding the molecular mechanisms of estrogen action. Using cDNA microarray examinations, 19 genes were identified as induced by 17-
-estradiol in MCF-7 cells, ten of which have been reported previously to be estrogen-responsive or to be linked with estrogen receptor status. Five known estrogen-regulated genes E2IG4, IGFBP4, SLC2A1, XBP1 and B4GALT1, and AFG3L1 responded quickly to estrogen treatment. A novel estrogen-responsive gene was identified and named EEIG1 for early estrogen-induced gene 1. EEIG1 was clearly induced by 17--estradiol within 2 h of treatment, and was widely responsive to a group of estrogenic compounds including natural and synthetic estrogens and estrogenic environmental compounds. EEIG1 was expressed in ER-positive but not in ER-negative breast cancer cell lines. EEIG1 expression was repressed by antiestrogens 4-OH-tamoxifen and ICI 182,780 but not by protein synthesis inhibitors cycloheximide and puromycin. These results provide evidence that some estrogenic compounds differentially enhance the transcription of estrogen-regulated genes and suggest a role for EEIG1 in estrogen action.
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