胃癌中组蛋白H3第4位赖氨酸及第27位赖氨酸乙酰化的表达及Wnt／β-连环蛋白信号通路活性改变对其表达水平的影响  

The expression of histone H3 lysine 4 acetylation and histone H3 lysine 27 acetylation and the effect to its expression for regulation of Wnt/β-catenin signaling pathway in gastric carcinoma

作　　者：李朝霞[1] 刘茜[1] 王蕊[1] 韩磊[2] 姜葵[1] 张庆瑜[1] 

机构地区：[1]天津医科大学总医院消化科,300052 [2]天津市神经病学研究所神经肿瘤实验室,300052

出　　处：《中华实验外科杂志》2016年第2期295-298,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金（81172356）;天津市基础重点基础科技项目基金（10jczdjc18500）

摘　　要：目的观察组蛋白H3第4位赖氨酸乙酰化（H3K4AC）及组蛋白H3第27位赖氨酸乙酰化（H3K27AC）在胃癌及正常胃黏膜组织中的表达，并分析与临床病理特征的关系，探讨Wnt／β-连环蛋白（β-catenin）信号通路与组蛋白乙酰化修饰之间的相互关系。方法首先利用组织芯片技术免疫组织化学的方法检测H3K4AC和H3K27AC在45例不同级别胃癌及其癌旁组织和10例正常胃黏膜组织中的表达。然后通过Western blot方法检测加入Wnt／β-catenin信号通路抑制剂FH535及激活剂Wnt3a后组蛋白乙酰化表达的变化。结果免疫组织化学结果显示H3K4AC在正常组织、癌旁组织及胃腺癌中表达阳性率分别为90．0％、88．9％、77．8％，H3K27AC表达阳性率分别为100．0％、95．6％、88．9％，结果提示与正常胃黏膜组织比较，胃癌组织中H3K4AC和H3K27AC表达水平明显下调（P〈0．05）；H3K4AC在高分化、中分化、低分化胃癌中表达阳性率分别为100．0％、91．7％、69．2％，H3K27AC表达阳性率分别为100．0％、91．7％、84．6％，差异有统计学意义（P〈0．05）。加入Wnt／β-catenin信号通路抑制剂后，H3K4AC及H3K27AC与对照组比较均出现表达下凋（P〈0．05），而加入该通路激活剂后，目的蛋白则表现为上升趋势。结论H3K4AC和H3K27AC在胃癌组织中呈低表达状态，并与肿瘤分化程度相关；Wnt／β-catenin信号通路活性改变可以调控组蛋白乙酰化的表达。Objective To investigate the expression of acetylation at lysine 4 of histone H3 （H3K4AC） and acetylation at lysine 27 of histone H3 （H3K27AC） in gastric cancer tissues and normal gastric tissues, and to evaluate its correlation with clinicopathological parameters of gastric carcinoma, then we explored the interrelation between Wnt/β- catenin pathway and histone acetylation modification. Methods Immunohistochemistry （IHC） was utilized to examine the expression of H3K4AC and H3K27AC in 45 gastric cancer specimens and 45 adjacent tissues of cancer and 10 normal gastric tissues, then we investigated the histone acetylation levels when the gastric cancer cells was treated with the inhitor （FH535） or activtor （Wnt3a） of Wnt/β-catenin pathway. Results Immunohistochemical analysis showed that the positive rate of H3K4AC in normal gastric mucosa, para -carcinoma tissue and gastric carcinoma tissue were 90. 0%, 88. 9%, 77. 8% respectively, and the positive rate of H3K27AC were 100. 0%, 95.6%, 88. 9% respectively, the results suggest that H3K4AC and H3K27AC expression significantly decreased in gastric cancer tissues compared to normal gastric tissues （P 〈 0. 05） ; The positive rate of H3KdAC in well - differentiated, middle - differentiated and poorly - differentiated gastric carcinoma were 100. 0%, 91.7%, 69. 2% respectively, and the positive rate of H3K27AC were 100. 0%, 91.7%, 84. 6% respectively, the difference was statistically significant （P 〈 0. 05 ）. The H3K4AC and H3K27AC expression showed a descending tendency when the inhibitor was added, and there was a reverse trend when the cells was treated with the activor. Conclusion Low expression of H3K4AC and H3K27AC was found in gastric cancer tissues and was correlated with the differentation; the regulation of Wnt/β- catenin pathway have an effect on the expression of histone acetylation.

关 键 词：组蛋白乙酰化 Wnt/β-连环蛋白信号通路 胃癌 

分 类 号：R730[医药卫生—肿瘤]