期刊
TUMOR BIOLOGY
卷 37, 期 10, 页码 13799-13809出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-016-5193-9
关键词
Esophageal squamous cell carcinoma; PKC iota; CDK7; Cell cycle; Proliferation
类别
资金
- National Natural Science Foundation of China [81171140, 81472272]
Protein kinase C iota (PKC iota) has been shown to play an important role in tumorigenesis of many cancers. It was reported that frequent amplification and overexpression of PKCi were correlated with resistance to anoikis in primary esophageal squamous cell carcinomas (ESCC). In this study, we clarified a novel role of PKC iota on the cell cycle progression and proliferation in ESCC. Western blot and immunohistochemistry (IHC) analysis showed that the expression of PKC iota was higher in ESCC tumor tissues and cell lines. Meanwhile, IHC stain revealed that PKC iota was positively correlated with clinical pathologic variables such as tumor size, tumor grade, and tumor invasion, as well as ki67. Immunoprecipitation and immunofluorescence assay revealed that PKC iota/CDK7 has the physical interaction and were co-located in the cell nucleus. And this direct interaction could increase the phosphorylation level of CDK7. In vitro studies such as starvation and refeeding assay along with PKC iota-shRNA transfection assay demonstrated that PKC iota expression promoted proliferation of ESCC cells. And knocking PKCi down by silencing RNA (siRNA) significantly caused cell cycle arrest at G0/G1 phase, decreased rate of colony formation, and alleviated cellular apoptosis. This research provide new insights into PKCi signaling to more deeply understand its cancer-promoting function in ESCC.
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