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Interleukin‐6 activates phosphatidylinositol‐3 kinase, which inhibits apoptosis in human prostate cancer cell lines
Author(s) -
Chung Theodore D.K.,
Yu Jianqing J.,
Kong Tony A.,
Spiotto Michael T.,
Lin James M.
Publication year - 2000
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(20000101)42:1<1::aid-pros1>3.0.co;2-y
Subject(s) - wortmannin , lncap , cancer research , cell growth , signal transduction , biology , tyrosine kinase , kinase , tyrosine phosphorylation , microbiology and biotechnology , prostate cancer , protein kinase b , medicine , cancer , biochemistry
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. Prostate 42:1–7, 2000. © 2000 Wiley‐Liss, Inc.