乳腺癌中蛋白高乙酰化/琥珀酰化水平及其同组蛋白2AX高表达的相关性

High protein acetylation/succinylation levels and their correlation with high histone 2AX expression level in breast cancer

目的明确乳腺癌中蛋白乙酰化/琥珀酰化修饰和组蛋白2AX(H2AX)表达水平,并确认两者之间是否具有相关性。方法Western blotting及RT-PCR方法检测11例乳腺癌组织和细胞中蛋白修饰和H2AX表达水平,并利用组蛋白去乙酰化酶抑制剂初步明确乙酰化和琥珀酰化可能存在的共同调控方式;载体构建及过表达方法明确H2AX表达同蛋白修饰之间的相关性。结果同正常乳腺组织相比,乳腺癌组织中蛋白乙酰化/琥珀酰化水平增加,且两者可能受组蛋白去乙酰化酶(HDAC)家族成员的共同调控。乳腺癌组织及细胞中H2AX mRNA及蛋白表达水平增加,且其表达水平同代表核仁磷蛋白1(NPM1)的表达及修饰水平成正相关。结论乳腺癌具有蛋白高乙酰化/琥珀酰化修饰及H2AX高表达的特点,且H2AX表达水平同部分蛋白修饰水平成正相关。

Objective To explore the protein acetylation/succinylation and histone 2 AX(H2AX)expression levels in breast cancer,as well as their correlation.Methods By Western blotting and RT-PCR methods to detect the protein modification and H2AX expression levels in 11 breast cancer tissues and cells,as well as to explore the common regulation way of protein acetylation and succinylation by treatment of histone deacetylase inhibitors;To study the relationship between H2AX expression level and protein modification level through the construction and over-expression of indicated plasmids.Results Compared with the adjacent normal tissues,there existed an increase protein acetylation/succinylation levels in breast cancer tissues,and the protein acetylation and succinylation were both regulated by histone deacetylase(HDAC)members.The H2AX mRNA and protein expression levels were increased both in breast cancer cell and tissues,its expression level and the expression and modification level of represented protein nucleophosmin 1(NPM1)showed a positive correlation.Conclusion The breast cancer possesses a characteristic of high protein acetylation/succinylation levels and high H2AX expression level,the H2AX expression level and the modification level of partial proteins in breast cancer have a positive correlation.