Epac1, PDE4, and PKC protein expression and their association with AKAP95, Cx43, and cyclinD2/E1 in breast cancer tissues

Abstract

BackgroundThis study was conducted to investigate the exchange protein directly activated by cAMP (Epac1), PDE4, and PKC expression in breast cancer tissues, and the correlation between these proteins and AKAP95, Cx43, cyclin D2, and cyclin E1.Methods PV‐9000 two‐step immunohistochemistry was used to analyze protein expression.ResultsThe positive rate of Epac1 protein expression in breast cancer tissues (58%) was higher than in para‐carcinoma tissues (10%) (P < 0.05). There were no significant differences in the positive rates of PDE4 and PKC expression between breast cancer and para‐carcinoma tissues (P > 0.05). The positive expression rate of PDE4 was higher in the P53 protein positive group compared to the P53 negative group (P < 0.05). Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins were observed (P < 0.05).Conclusion Epac1 expression in breast cancer tissues was increased, suggesting that the protein may be involved in the development of breast cancer. Correlations between Epac1 and cyclin D2, PDE4 and cyclin D2, AKAP95 and PKC, Cx43 and PKC, and cyclin D2 and PKC proteins suggested synergistic effects among these proteins in the development of breast cancer.

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

“…In addition, pharmacological inhibition of EPAC1 by ESI-09 suppresses cell proliferation and migration, while inducing cell cycle arrest and apoptosis in breast cancer cells (567). Increased expression of EPAC1 in 58% of breast cancer patients (29/ 50) was reported, as compared with a 10% positive rate (1/10) in controls (446). These studies demonstrate fresh and exciting potentials for novel therapeutic strategies targeting EPAC1 in breast and gastric/esophagus cancer treatments.…”

Sodium Arsenite Induces Bronchial Epithelial Cell Cancer With Mitochondrial Dysfunction by Affecting Cell Cycle

“…Existing immune histochemical results of our laboratory [19][20][21] showed that the expression of AKAP95, cyclin D1, cyclin D2 and cyclin E1 in cancer tissues was higher than that in adjacent tissues, and expression of above proteins was correlated. CCNDs and CCNEs are considered as proto-oncogenes, and cyclin Ds and cyclin Es are mainly synthesized and play a role in G1 phase [22,23].…”

The Role of Neuropeptide-Stimulated cAMP-EPACs Signalling in Cancer Cells

“…However, several research reported that EPAC1 depict a protective role in glioblastoma [ 62 , 63 , 64 ], bladder cancer [ 65 ] and renal cancer [ 66 ]. What’s more, EPAC1 can either promote or attenuate cancer progression in breast cancer [ 67 , 68 , 69 ], leukaemia [ 70 , 71 ], neuroendocrine cancer [ 72 ], ovarian cancer [ 73 , 74 , 75 , 76 ] and prostate cancer [ 77 , 78 , 79 , 80 ]. The reason for dual functions of EPAC1 in the same cancer is very complicated and can be influenced by cancer cell types as well as genomic and transcriptomic differences, but the integrated mechanism remains elusive.…”

“…The expression level of EPAC1 is associated with breast cancer patient prognosis [ 68 ]. The protein level of EPAC1 in breast cancer tissues was significantly upregulated versus para-carcinoma tissues.…”