Convergent Transcriptional Profiles Induced by Endogenous Estrogen and Distinct Xenoestrogens in Breast Cancer Cells

Carcinogenesis. 2006 Aug;27(8):1567-78. doi: 10.1093/carcin/bgi339. Epub 2006 Feb 10.

Abstract

Estrogen receptors display high levels of promiscuity in accommodating a wide range of ligand structures, but the functional consequence of changing receptor conformations in complex with distinct agonists is highly controversial. To determine variations in the transactivation capacity induced by different estrogenic agonists, we assessed global transcriptional profiles elicited by natural or synthetic xenoestrogens in comparison with the endogenous hormone 17beta-estradiol. Human MCF7 and T47D carcinoma cells, representing the most frequently used model systems for tumorigenic responses in the mammary gland, were synchronized by hormone starvation during 48 h. Subsequently, a 24 h exposure was carried out with equipotent concentrations of the selected xenoestrogens or 17beta-estradiol. Analysis of messenger RNA was performed on high-density oligonucleotide microarrays that display the sequences of 33,000 human transcripts, yielding a total of 181 gene products that are regulated upon estrogenic stimulation. Surprisingly, genistein (a phytoestrogen), bisphenol-A and polychlorinated biphenyl congener 54 (two synthetic xenoestrogens) produced highly congruent genomic fingerprints by regulating the same range of human genes. Also, the monotonous genomic signature observed in response to xenoestrogens is identical to the transcriptional effects induced by physiological concentrations of 17beta-estradiol. This striking functional convergence indicates that the transcription machinery is largely insensitive to the particular structure of estrogen receptor agonists. The occurrence of such converging transcriptional programs reinforces the hypothesis that multiple xenoestrogenic contaminants, of natural or anthropogenic origin, may act in conjunction with the endogenous hormone to induce additive effects in target tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Benzhydryl Compounds
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Environmental Pollutants / pharmacology
  • Estradiol / pharmacology*
  • Estrogens, Non-Steroidal / pharmacology
  • Gene Expression Profiling*
  • Genistein / pharmacology*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phenols / pharmacology*
  • Polychlorinated Biphenyls / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzhydryl Compounds
  • Biomarkers, Tumor
  • Environmental Pollutants
  • Estrogens, Non-Steroidal
  • Phenols
  • Estradiol
  • Polychlorinated Biphenyls
  • Genistein
  • bisphenol A