原癌基因酪氨酸蛋白激酶Src
癌症研究
生物
绒毛膜癌
细胞生长
细胞周期蛋白D1
酪氨酸磷酸化
磷酸化
内科学
内分泌学
细胞周期
细胞
细胞生物学
医学
生物化学
作者
Wei Wu,Yao Wang,Yin Xu,Yahui Liu,Yudong Wang,H Zhang
出处
期刊:Placenta
[Elsevier]
日期:2014-10-01
卷期号:35 (10): 824-830
被引量:11
标识
DOI:10.1016/j.placenta.2014.07.012
摘要
Gestational trophoblastic disease (GTD) is a heterogeneous group of pregnancy-related disorders. Hydatidiform mole (HM) is the most common type of GTD, whereas gestational choriocarcinoma is the most aggressive. Non-receptor tyrosine kinase c-Src contributes to the transformation to a malignant phenotype in various cancers. However, the role of c-Src in the pathogenesis of GTD remains largely unknown.The expression level of phosphorylated c-Src was determined by immunohistochemistry and Western blotting assay. JAR and JEG-3 cells were treated with hCG, specific c-Src inhibitor saracatinib and PP2, and PKA specific inhibitor, PKI. Cell growth rate and cell migration/invasion ability was determined by cell proliferation and transwell assays respectively.c-Src was highly activated in HM tissues and choriocarcinoma cells (JAR and JEG-3). c-Src was activated by hCG in a time and concentration-dependent manner, which was abrogated by specific c-Src and PKA inhibitors. Inhibition of c-Src activity in JAR and JEG-3 cells by saracatinib leaded to a decrease in the rate of cell growth and cell migration/invasion ability. Furthermore, inhibition of c-Src phosphorylation induced cell cycle arrest and reduced expressions of cyclin A2, cyclin B1, cyclin E1, FOXD3 and NANOG. Moreover, inhibition of c-Src activity resulted in decreased p-FAK(Tyr397) phosphorylation.Our findings indicate an important role of c-Src in the pathogenesis of GTD, and we propose that c-Src inhibitors are potential adjuvant chemotherapeutic drugs for the treatment of GTD.
科研通智能强力驱动
Strongly Powered by AbleSci AI