title: Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.
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.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637, USA. tchung@midway.uchicago.edu
authors.forename: T D
authors.initials: TD
authors.lastname: Chung
authors.forename: J J
authors.initials: JJ
authors.lastname: Yu
authors.forename: T A
authors.initials: TA
authors.lastname: Kong
authors.forename: M T
authors.initials: MT
authors.lastname: Spiotto
authors.forename: J M
authors.initials: JM
authors.lastname: Lin
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin