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Role of the ProteinTyrosine Phosphatase SHP-I in Interleukin-6 Regulation of Prostate Cancer Cells

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Author

  • Helena Tassidis
  • Zoran Culig
  • Anette Gjörloff Wingren
  • Pirkko Härkönen

Summary, in English

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. (C) 2010 Wiley-Liss, Inc.

Publishing year

2010

Language

English

Pages

1491-1500

Publication/Series

The Prostate

Volume

70

Issue

14

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Obstetrics, Gynecology and Reproductive Medicine

Keywords

  • prostate cancer cells
  • apoptosis
  • proliferation
  • IL-6
  • PTEN

Status

Published

ISBN/ISSN/Other

  • ISSN: 0270-4137
  • http://www.ncbi.nlm.nih.gov/pubmed/20687222?dopt=Abstract