Stress hormones regulate interleukin-6 expression by human ovarian carcinoma cells through a Src-dependent mechanism

J Biol Chem. 2007 Oct 12;282(41):29919-26. doi: 10.1074/jbc.M611539200. Epub 2007 Aug 23.

Abstract

Recent studies have demonstrated that chronic stress promotes tumor growth, angiogenesis, and metastasis. In ovarian cancer, levels of the pro-angiogenic cytokine, interleukin 6 (IL-6), are known to be elevated in individuals experiencing chronic stress, but the mechanism(s) by which this cytokine is regulated and its role in tumor growth remain under investigation. Here we show that stress hormones such as norepinephrine lead to increased expression of IL-6 mRNA and protein levels in ovarian carcinoma cells. Furthermore, we demonstrate that norepinephrine stimulation activates Src tyrosine kinase and this activation is required for increased IL-6 expression. These results demonstrate that stress hormones activate signaling pathways known to be critical in ovarian tumor progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / metabolism
  • Mice
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Norepinephrine / metabolism*
  • Ovarian Neoplasms / metabolism*
  • src-Family Kinases / metabolism*

Substances

  • Interleukin-6
  • src-Family Kinases
  • Norepinephrine