Cross-talk between endocrine-disrupting chemicals and cytokine signaling through estrogen receptors

Biochem Biophys Res Commun. 2004 Mar 12;315(3):692-8. doi: 10.1016/j.bbrc.2004.01.109.

Abstract

STAT3 mainly acts as a signal transducer of IL-6 family cytokines and transcriptionally activates specific target genes. STAT3 has also been demonstrated to mediate cellular transformation and is found in numerous cancers. Endocrine-disrupting chemicals (EDCs) are a diverse group of chemicals that bind to estrogen receptors (ERs), mimic estrogenic actions, and may have adverse effects on human health. In our previous study, we demonstrated that estrogens suppressed the STAT3-mediated transcription activity through ERs. In this study, we examined the effects of EDCs on STAT3-mediated signaling through ERs. Surprisingly, some of EDCs enhanced STAT3-mediated transcription activity through ERs. This finding strongly suggests that EDCs may play an important role in the endocrine functions by mimicking cytokine activity by stimulating STAT3 actions through ERs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytokines / metabolism
  • Cytokines / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Endocrine System / drug effects*
  • Endosulfan / metabolism
  • Estrogen Receptor Modulators / pharmacology
  • Humans
  • Interleukin-6 / pharmacology
  • Leukemia Inhibitory Factor
  • Luciferases / metabolism
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Methoxychlor / metabolism
  • NF-kappa B / metabolism
  • Phenols / metabolism
  • Phosphorylation
  • Receptor Cross-Talk / drug effects
  • Receptor Cross-Talk / physiology*
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / metabolism*
  • STAT3 Transcription Factor
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tamoxifen / pharmacology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology
  • Transfection

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Estrogen Receptor Modulators
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • NF-kappa B
  • Phenols
  • Receptors, Estrogen
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • Tamoxifen
  • Luciferases
  • Endosulfan
  • Methoxychlor