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

被引:9
|
作者
Meng, Fei [1 ]
Zhao, Xiaoyun [2 ]
Zhang, Shulan [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Obstet & Gynecol, Shenyang 110004, Liaoning Provin, Peoples R China
[2] Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Dept Microbiol & Cell Biol, Shenyang, Liaoning Provin, Peoples R China
基金
中国国家自然科学基金;
关键词
cell proliferation; cervical cancer; SH2-containing protein tyrosine phosphatase 2; type I interferon ss; TYROSINE-PHOSPHATASE; RETINOIC ACID; IFN-BETA; EXPRESSION; ALPHA; CARCINOMA; INVOLVEMENT; TLR4;
D O I
10.1111/j.1447-0756.2012.01952.x
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
Aim: 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. Material and Methods: A total of 45 patients with cervical cancer (stage IIII), 32 with cervical intraepithelial neoplasia and 20 healthy subjects were consecutively recruited. The levels of SHP-2 and interferon (IFN)-beta 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-beta 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-beta 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-beta (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-beta production.
引用
收藏
页码:272 / 279
页数:8
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