PKC iota promotes cellular proliferation by accelerated G1/S transition via interaction with CDK7 in esophageal squamous cell carcinoma.

Abstract

Protein kinase C iota (PKCι) 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 PKCι on the cell cycle progression and proliferation in ESCC. Western blot and immunohistochemistry (IHC) analysis showed that the expression of PKCι was higher in ESCC tumor tissues and cell lines. Meanwhile, IHC stain revealed that PKCι 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 PKCι/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 PKCι-shRNA transfection assay demonstrated that PKCι 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.

• Authors: Sujie Ni, Lingling Chen, Mei Li, Weijuan Zhao, Xiaohang Shan, Miaomiao Wu, Jialin Cheng, Li Liang, Yayun Wang, Wenyan Jiang, Jianguo Zhang, Runzhou Ni
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 10 Pg. 13799-13809 (Oct 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 27481515 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Isoenzymes
• RNA, Messenger
• Protein Kinase C
• protein kinase C lambda
• Cyclin-Dependent Kinases

Topics

• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Carcinoma, Squamous Cell (genetics, metabolism, secondary)
• Cell Proliferation
• Cyclin-Dependent Kinases (genetics, metabolism)
• Esophageal Neoplasms (genetics, metabolism, pathology)
• Female
• Flow Cytometry
• Follow-Up Studies
• G1 Phase
• Humans
• Immunoenzyme Techniques
• Isoenzymes (genetics, metabolism)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Protein Kinase C (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• S Phase
• Signal Transduction
• Survival Rate
• Tumor Cells, Cultured