Sun Qian, Wang Dai, Ai Ganghao, Tian Longben, Zhao Long, Chen Renzhen, Wang Kai, Guo Dongbei, Yao Youliang, Liu Wenzhi, Kong XIangyu, Chen Xiaoxuan, Zhang Yongxing
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian,361102, PR China.
Folia Histochem Cytobiol. 2018;56(1):21-26. doi: 10.5603/FHC.a2018.0004. Epub 2018 Mar 12.
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.
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.
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.
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.
环磷腺苷（cAMP）直接激活的交换蛋白1（Epac1）作为第二信使cAMP的下游靶点，可单独或与蛋白激酶A（PKA）协同调节cAMP的多种生物学效应。Epac1是促进蛋白激酶C（PKC）易位和激活所必需的。本研究旨在评估肺癌组织和癌旁组织中Epac1和蛋白激酶C（PKC）的免疫反应强度，以及它们与临床病理指标的相关性。同时还检测了Epac1、PKC、A激酶锚定蛋白95（AKAP95）和连接蛋白43（Cx43）免疫反应性之间的相关性。
采用PV-9000两步免疫组化技术，检测46例肺癌组织样本和12例相邻癌旁标本中Epac1、Cx43的免疫表达水平，以及45例肺癌组织样本和12例相邻癌旁标本中PKC、AKAP95的免疫表达水平。
肺癌组织中Epac1阳性样本的百分比显著低于相邻癌旁标本（37%对83.3%，p<0.05）；PKC免疫反应性的差异不显著（64.4%对91.7%）。Epac1表达与恶性程度和淋巴结转移相关（P<0.05），但与组织学类型无关（P>0.05），而PKC表达与这些参数无关。有趣的是，Epac1表达与PKC和Cx43表达相关。此外，PKC表达与AKAP95表达相关。
正常的Epac1表达可能抑制肺癌的发生和转移，其下调通过PKC和Cx调节参与肺癌细胞周期进程。
