1. Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.
- Author
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Sun Q, Wang D, Ai G, Tian L, Zhao L, Chen R, Wang K, Guo D, Yao Y, Liu W, Kong X, Chen X, and Zhang Y
- Subjects
- Adult, Aged, Connexin 43 metabolism, Humans, Middle Aged, Protein Kinase C metabolism, Cell Cycle genetics, Connexin 43 genetics, Guanine Nucleotide Exchange Factors metabolism, Lung Neoplasms physiopathology, Protein Kinase C genetics
- Abstract
Introduction: The exchange protein directly activated by cAMP (Epac1), a downstream target of the second messenger cAMP, modulates multiple biological effects of cAMP, alone or in cooperation with protein kinase A (PKC). Epac1 is necessary for promoting protein kinase C (PKC) translocation and activation. The aim of the study was to assess the intensity of Epac1 and protein kinase C (PKC) immunoreactivity in lung cancer and para-carcinoma tissues, and their associations with clinical-pathological indexes. Correlations between the immunoreactivity of Epac1, PKC, A-kinase anchor protein 95 (AKAP95) and connexin43 (Cx43) were also examined., Material and Methods: Epac1, Cx43 (46 cases) and PKC, AKAP95 (45 cases) immunoexpression levels were determined in tissue samples of lung cancer and in 12 samples of neighboring para-carcinoma specimens by the PV-9000 Two-step immunohistochemical technique., Results: The percentage of Epac1 positive samples was significantly lower in lung cancer tissue than in neighboring para-carcinoma specimens (37% vs. 83.3%, p < 0.05); the difference in PKC immunoreactivity was not significant (64.4% vs. 91.7%). Epac1 expression was associated with the degree of malignancy and lymph node metastasis (P < 0.05), but not with histological type (P > 0.05), whereas PKC expression was not related to these parameters. Interestingly, Epac1 expression was correlated with PKC and Cx43 expression. Moreover, PKC expression was correlated with AKAP95 expression., Conclusion: Normal Epac1 expression may suppress lung cancer occurrence and metastasis, and its downregulation is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.
- Published
- 2018
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