Role of protein tyrosine phosphatase SHP-1 in interleukin-6 regulation of prostate cancer

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 favourable outcome for prostate cancer patients. Methods Parental LNCaP and 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 SHP-I, PTEN, STAT3, pSTAT3, ERK, pERK, AKT, pAKT, PTEN and SHP-1 was analysed by immunohistochemistry, Western blot, cDNA microarray quantitative PCR and reverse transcriptase PCR. Proliferation and apoptosis of transfected cells was analysed with caspase3/7 and flow cytometry. Results Phosphorylation of ERK and STAT3 was increased in the LNCaP-IL6+ subline compared to LNCaP cells, whereas pAkt was decresaed. This could be due tore-expression of PTEN in LNCaP-IL6+ cells. Overexpression and inhibition experiments with SHP-1 siRNA showed that SHP-1 reduced proliferation and increased apoptosis in both cell lines. A cDNA analysis revealed 80 up-regulated and 87 down-regulated SHP-1 related genes in the LNCaP-IL6+ cell line compared to LNCaP cells. Conclusions SHP-1 suppresses growth and increases apoptosis in both LNCaP and LNCaP-IL6+ cells which suggests that SHP-1 could provide a therapeutic target for the prostate cancer cells even in the case that have gained an IL-6 related growth advantage