Abstract
Estrogen receptors (ERs) 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 beta-estradiol in MCF-7 cells, 10 of which have been reported previously to be estrogen responsive or to be linked with ER 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 EEIG1for early estrogen-induced gene 1. EEIG1 was clearly induced by 17 beta-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Breast Neoplasms / genetics
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Cycloheximide / pharmacology
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DNA-Binding Proteins / genetics
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Dose-Response Relationship, Drug
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Estradiol / analogs & derivatives*
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Estradiol / pharmacology
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Estrogen Antagonists / pharmacology
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Estrogens / pharmacology*
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Female
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Fulvestrant
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Galactosyltransferases / drug effects
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Galactosyltransferases / genetics
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Gene Expression Regulation / drug effects*
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Humans
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Insulin-Like Growth Factor Binding Protein 4 / drug effects
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Insulin-Like Growth Factor Binding Protein 4 / genetics
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Neoplasm Proteins / drug effects
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Neoplasm Proteins / genetics*
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Nuclear Proteins / genetics
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Oligonucleotide Array Sequence Analysis / methods*
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Pesticides / pharmacology
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Phytoestrogens / pharmacology
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Protein Synthesis Inhibitors / pharmacology
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Puromycin / pharmacology
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Receptors, Estrogen / drug effects
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Receptors, Estrogen / genetics
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Receptors, Estrogen / metabolism
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Regulatory Factor X Transcription Factors
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Tamoxifen / analogs & derivatives*
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Tamoxifen / pharmacology
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Transcription Factors
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Tumor Cells, Cultured
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X-Box Binding Protein 1
Substances
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DNA-Binding Proteins
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Estrogen Antagonists
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Estrogens
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Insulin-Like Growth Factor Binding Protein 4
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Neoplasm Proteins
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Nuclear Proteins
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Pesticides
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Phytoestrogens
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Protein Synthesis Inhibitors
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Receptors, Estrogen
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Regulatory Factor X Transcription Factors
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Transcription Factors
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X-Box Binding Protein 1
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XBP1 protein, human
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Tamoxifen
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afimoxifene
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Fulvestrant
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Puromycin
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Estradiol
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Cycloheximide
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Galactosyltransferases
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beta-1,4-galactosyltransferase I