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Role of the protein tyrosine phosphatase SHP‐1 in Interleukin‐6 regulation of prostate cancer cells
Author(s) -
Tassidis Helena,
Culig Zoran,
Wingren Anette Gjörloff,
Härkönen Pirkko
Publication year - 2010
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/pros.21184
Subject(s) - lncap , cancer research , biology , cytokine , cell growth , prostate cancer , mapk/erk pathway , protein kinase b , apoptosis , stat3 , signal transduction , cancer , immunology , microbiology and biotechnology , biochemistry , genetics
BACKGROUND Interleukin‐6 (IL‐6) is a multifunctional cytokine that has been implicated in the modulation of growth and progression of prostate cancer. Decreased expression of the tyrosine phosphatase SHP‐1, involved in regulation of cytokine and tyrosine kinase receptor signaling, has been shown to be associated with less favorable outcome among prostate cancer patients. METHODS Parental LNCaP cells and an LNCaP‐IL6+ subline, derived from parental LNCaP cells by continuous culture of the cells in the presence of recombinant IL‐6 were used in the study. Expression of STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN, and SHP‐1 was analyzed by immunohistochemistry, Western blots, cDNA microarray, quantitative PCRs, and reverse transcriptase PCRs. Proliferation and apoptosis of transfected cells were analyzed by caspase3/7 assay and flow cytometry. RESULTS Phosphorylation of ERK and STAT3 was increased in the LNCaP‐IL6+ subline compared with LNCaP cells, whereas pAKT was decreased. Overexpression and inhibition experiments with SHP‐1 siRNA showed that SHP‐1 reduced proliferation and increased apoptosis in both cell lines. Microarray analysis revealed 80 up‐regulated and 87 down‐regulated SHP‐1‐related genes in the LNCaP‐IL6+ cell line compared with LNCaP cells. CONCLUSIONS SHP‐1 suppresses growth and increases apoptosis in both LNCaP and LNCaP‐IL6+ cells, which suggests that SHP‐1 could be a therapeutic target in prostate cancer, even when there is an IL‐6‐related growth advantage. Prostate 70: 1491–1500, 2010. © 2010 Wiley‐Liss, Inc.