Identification of estrogen-responsive genes by complementary deoxyribonucleic acid microarray and characterization of a novel early estrogen-induced gene: EEIG1

Mol Endocrinol. 2004 Feb;18(2):402-11. doi: 10.1210/me.2003-0202. Epub 2003 Nov 6.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Cycloheximide / pharmacology
  • DNA-Binding Proteins / genetics
  • Dose-Response Relationship, Drug
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Estrogens / pharmacology*
  • Female
  • Fulvestrant
  • Galactosyltransferases / drug effects
  • Galactosyltransferases / genetics
  • Gene Expression Regulation / drug effects*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 4 / drug effects
  • Insulin-Like Growth Factor Binding Protein 4 / genetics
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / genetics*
  • Nuclear Proteins / genetics
  • Oligonucleotide Array Sequence Analysis / methods*
  • Pesticides / pharmacology
  • Phytoestrogens / pharmacology
  • Protein Synthesis Inhibitors / pharmacology
  • Puromycin / pharmacology
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Regulatory Factor X Transcription Factors
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology
  • Transcription Factors
  • Tumor Cells, Cultured
  • X-Box Binding Protein 1

Substances

  • DNA-Binding Proteins
  • Estrogen Antagonists
  • Estrogens
  • Insulin-Like Growth Factor Binding Protein 4
  • Neoplasm Proteins
  • Nuclear Proteins
  • Pesticides
  • Phytoestrogens
  • Protein Synthesis Inhibitors
  • Receptors, Estrogen
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Tamoxifen
  • afimoxifene
  • Fulvestrant
  • Puromycin
  • Estradiol
  • Cycloheximide
  • Galactosyltransferases
  • beta-1,4-galactosyltransferase I