Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1.
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.
Wang
Dong-Yu
DY
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario M5S 3E5, Canada.
Fulthorpe
Roberta
R
Liss
Steven N
SN
Edwards
Elizabeth A
EA
D001943:Breast Neoplasms / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D005700:Galactosyltransferases / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000187:drug effects / Q000235:genetics; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010575:Pesticides / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D004967:Estrogens; D018974:Insulin-Like Growth Factor Binding Protein 4; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010575:Pesticides; D048789:Phytoestrogens; D011500:Protein Synthesis Inhibitors; D011960:Receptors, Estrogen; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; D011691:Puromycin; D004958:Estradiol; D003513:Cycloheximide; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I