PDE4 and Epac1 Synergistically Promote Rectal Carcinoma via the cAMP Pathway.

OBJECTIVE: To assess the expression levels of exchange protein 1 directly activated by cAMP (Epac1) and phosphodiesterase 4 (PDE4) in rectal carcinoma, and their associations with clinicopathological indexes. In addition, the associations of PDE4 and Epac1 with A-kinase anchor protein 95, connexin 43, cyclin D1, and cyclin E1 were evaluated. METHODS: The PV-9000 two-step immunohistochemistry method was used to determine protein expression in 44 rectal carcinoma tissue samples and 16 paracarcinoma tissue specimens. RESULTS: The positive rate of PDE4 protein expression in rectal carcinoma tissues was higher than that of paracarcinoma tissues (59.09% vs. 12.5%, P < 0.05). Similar findings were obtained for Epac1 (55% vs. 6.25%, P < 0.05). No significant associations of PDE4 and Epac1 with degree of differentiation, histological type, and lymph node metastasis were found in rectal carcinoma (P > 0.05). Correlations between PDE4 and Epac1, PDE4 and Cx43, PDE4 and cyclin E1, and Epac1 and Cx43 were observed (all P < 0.05). There was no correlation between the other protein pairs examined (P > 0.05). CONCLUSION: PDE4 and Epac1 expression levels are increased in rectal carcinoma tissues, suggesting that the two proteins may be involved in the development of this malignancy. Meanwhile, correlations between PDE4 and Epac1, PDE4 and Cx43, PDE4 and cyclin E1, and Epac1 and Cx43 suggested synergistic effects of these proteins in promoting rectal carcinoma.

Epac1 is involved in cell cycle progression in lung cancer through PKC and Cx43 regulation.

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.