SHP-2 phosphatase promotes cervical cancer cell proliferation through inhibiting interferon-β production.

OBJECTIVE

The aim of this study was to explore the effect of Src-homology-2-domain-containing protein, tyrosine phosphatase 2 (SHP-2) on the proliferation of cervical cancer cells.

METHODS

A total of 45 patients with cervical cancer (stage I-III), 32 with cervical intraepithelial neoplasia and 20 healthy subjects were consecutively recruited. The levels of SHP-2 and interferon (IFN)-β expression in cervical tissues were characterized by immunohistochemistry and statistically analyzed by logistic regression. Following knockdown of SHP-2 expression by a siRNA or pre-treatment with a specific peptide, the effect of SHP-2 expression in THP-1 cells on the growth and survival of SiHa cells and on IFN-β production was determined by co-culture assays, 3-(4,5)-dimethylthiazol (-z-y 1)-3,5-diphenyltetrazolium bromide, and enzyme immunosorbent assay.

RESULTS

The levels of SHP-2 expression in cervical cancer tissues were significantly higher than that in cervical intraepithelial neoplasia and uterine myoma tissues (P<0.05, respectively), and negatively correlated with the levels of IFN-β expression in these tissues (R=-0.582, P<0.05). Knockdown of SHP-2 expression with SHP-2 siRNA or treatment with the SHP-2-specific blocking peptide in THP-1 cells significantly increased the production of IFN-β (P<0.05, respectively) and inhibited the proliferation of SiHa cells in a co-culture system of THP-1 and SiHa cells (P<0.05, respectively).

CONCLUSIONS

SHP-2 phosphatase promotes cervical cancer cell proliferation through inhibiting IFN-β production.