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

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

Forskningsoutput: TidskriftsbidragArtikelPeer review

20 Citeringar (Scopus)

Sammanfattning

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.

OriginalspråkEngelska
Sidor (från-till)1491-1500
Antal sidor9
TidskriftThe Prostate
Volym70
Utgåva14
DOI
StatusPublicerad - 2010
Externt publiceradJa

Nationell ämneskategori

  • Cancer och onkologi (30203)

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