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Role of the protein tyrosine phosphatase SHP-1 in Interleukin-6 regulation of prostate cancer cells.

AbstractBACKGROUND:
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.
AuthorsHelena Tassidis, Zoran Culig, Anette Gjörloff Wingren, Pirkko Härkönen
JournalThe Prostate (Prostate) Vol. 70 Issue 14 Pg. 1491-500 (Oct 01 2010) ISSN: 1097-0045 [Electronic] United States
PMID20687222 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright(c) 2010 Wiley-Liss, Inc.
Chemical References
  • DNA Primers
  • Interleukin-6
  • STAT3 Transcription Factor
  • Extracellular Signal-Regulated MAP Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Caspase 3
  • Caspase 7
Topics
  • Caspase 3 (metabolism)
  • Caspase 7 (metabolism)
  • Cell Division
  • Cell Line, Tumor
  • DNA Primers
  • Disease Progression
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Humans
  • Immunohistochemistry (methods)
  • Interleukin-6 (physiology)
  • Kinetics
  • Lymphatic Metastasis (genetics, pathology)
  • Male
  • PTEN Phosphohydrolase (genetics)
  • Prostatic Neoplasms (enzymology, genetics, pathology, physiopathology)
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor (metabolism)
  • Up-Regulation

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