Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines

Prostate. 2000 Jan;42(1):1-7. doi: 10.1002/(sici)1097-0045(20000101)42:1<1::aid-pros1>3.0.co;2-y.

Abstract

Background: A number of recent studies have identified interleukin (IL)-6 as an important regulator of prostate cancer growth. Here, we investigate the potential interaction of IL-6 with phosphatidylinositol (PI)-3 kinase, a key growth regulatory enzyme, in prostate cancer cell lines.

Methods: Tyrosine phosphorylation of p85, the regulatory subunit of PI-3 kinase, in the human prostate cancer cell lines LNCaP and PC-3 was assessed by sequential immunoprecipitation with anti-p85 antibody and immunoblotting with anti-phosphotyrosine. The effects of wortmannin, an inhibitor of PI-3 kinase, and/or IL-6 on cell growth were assessed by MTT assays. DNA laddering experiments were performed to assay for programmed cell death.

Results: Tyrosine phosphorylation of p85 is upregulated by IL-6 in both LNCaP and PC-3. IL-6 promotes coprecipitation of p85 with gp130, the signal-transducing component of the IL-6 receptor. Inhibition of PI-3 kinase with wortmannin induces programmed cell death in PC-3 cells. In contrast, wortmannin has no effect on LNCaP growth when used alone; however, combined with IL-6, wortmannin promotes apoptosis in these cells.

Conclusions: PI-3 kinase is involved in IL-6 signal transduction and delivers an antiapoptotic signal in human prostate cancer cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Enzyme Activation / physiology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Interleukin-6 / pharmacology*
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Interleukin-6
  • Phosphoinositide-3 Kinase Inhibitors
  • Wortmannin