Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.
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.
Chung
T D
TD
Department of Radiation and Cellular Oncology, University of Chicago, Chicago, Illinois 60637, USA. tchung@midway.uchicago.edu
Yu
J J
JJ
Kong
T A
TA
Spiotto
M T
MT
Lin
J M
JM
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
D000730:Androstadienes; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin