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Role of the protein tyrosine phosphatase SHP-1 in Interleukin-6 regulation of prostate cancer cells
Lund University.ORCID iD: 0000-0003-4190-5431
Österrike.
Lund University.
Lund University.
2010 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 70, no 14, 1491-1500 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 70, no 14, 1491-1500 p.
Keyword [en]
IL-6, PTEN, proliferation, apoptosis, prostate cancer cells
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:hkr:diva-15678DOI: 10.1002/pros.21184PubMedID: 20687222OAI: oai:DiVA.org:hkr-15678DiVA: diva2:952012
Funder
Swedish Cancer SocietyKnut and Alice Wallenberg Foundation
Available from: 2016-08-11 Created: 2016-08-11 Last updated: 2016-08-11Bibliographically approved

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CiteExportLink to record
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