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

Xiangyu Kong,Dai Wang,Youliang Yao,Yongxing Zhang,Kai Wang,Ganghao Ai,Fengjie Qi,Wenzhi Liu,Guiye Liang,Renzhen Chen,Dongbei Guo

doi:10.1155/2019/7145198

Abstract

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.

Highlights

Signal transduction is a necessary process for cells to achieve normal physiological processes
We previously assessed rectal carcinoma tissues and found higher positive rates of AKAP95, cyclin E1, and cyclin D1 compared with paracarcinoma tissues
phosphodiesterase 4 (PDE4) and Epac1 protein levels were further assessed in rectal cancer samples

Summary

Introduction

Signal transduction is a necessary process for cells to achieve normal physiological processes. PKA, which is a downstream of cAMP signal pathway, is an important protein kinase. AKAP95 is a PKA-anchored protein that anchors PKA RII subunits; the anchored PKA can catalytically target protein phosphorylation, ensuring and expanding signal transduction by the cAMP pathway [2, 3]. Cyclin D and cyclin E proteins can promote cell proliferation at the G1 phase in mammalians, while AKAP95 as an intermediary can help cyclin D/E and PKA RII subunits from the cyclin D/E-. The Epac protein includes two subtypes, i.e., Epac and Epac, both of which are expressed in many tissues and organs [6, 7]. Studies mentioned that Epac can regulate Cx43 to promote gap junction formation and intercellular communication [10]

Methods

Results

Conclusion