南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (04): 477-.doi: 10.12122/j.issn.1673-4254.2019.04.15

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G9a在乳腺癌中的表达及其对乳腺癌细胞增殖的影响

赵子超,刘奇伦,伍春梅,郭文静,李金平   

  • 出版日期:2019-04-20 发布日期:2019-04-20

Expression of G9a in breast cancer and its effect on proliferation of breast cancer cells in vitro

  • Online:2019-04-20 Published:2019-04-20

摘要: 目的探讨G9a在人乳腺癌中表达情况和分析其与乳腺癌临床病理学特征的关系及其对乳腺癌细胞增殖的影响。方法 收集2016年10月~2017年10月期间行手术治疗且临床资料齐全的122例乳腺癌组织及与之相对应的癌旁正常组织标本61例, 均提取于宁夏医科大学总医院生物样本组织库。利用免疫组化(IHC)和实时荧光定量PCR方法检测G9a在乳腺癌组织中的表 达情况;分析G9a与乳腺癌临床病理特征的关系;分析G9a与乳腺癌分子分型、免疫组化指标之间的关系;利用生物信息学方法 分析G9a在乳腺中的表达及对预后的影响;应用G9a抑制剂UNC0631检测G9a对乳腺癌细胞增殖的影响。结果(1)结合IHC、 实时荧光定量PCR及生信方法,发现G9a在人乳腺癌组织中呈高表达;(2)分析G9a与乳腺癌临床病理特征的关系中发现G9a 在乳腺浸润性导管癌组织中呈高表达,G9a的表达与乳腺癌患者的年龄呈负相关(均P<0.05);(3)分析G9a与乳腺癌分子分型、 免疫组化指标的关系中,发现G9a在Her-2过表达型乳腺癌中呈高表达,G9a的表达与Her-2、Ki-67及E-cadherin的表达呈正相 关(均P<0.05);(4)利用生信分析G9a与乳腺癌预后关系中发现G9a可作为乳腺癌预后不良的独立风险因素;(5)在应用G9a抑 制剂的实验中发现G9a抑制剂可抑制乳腺癌细胞的增殖。结论乳腺癌组织中G9a呈高表达,且促进乳腺癌的发生发展,可作 为乳腺癌预后不良的独立风险因素,可为乳腺癌的早期诊断和治疗提供新的方向。

Abstract: Objective To study the expression of G9a in human breast cancer, its association with the clinicopathological characteristics of breast cancer, and its effect on the proliferation of breast cancer cells. Methods A total of 122 specimens of breast cancer tissues and 61 adjacent normal tissues resected between October, 2016 and October, 2017 were obtained from the Tissue Bank of Ningxia Medical University General Hospital. Immunohistochemistry and real-time PCR were used to detect the expression of G9a in the breast cancer tissues. The relationship of G9a with the clinicopathological features of the patients, molecular subtypes of breast cancer and the immunohistochemical markers was analyzed. A bioinformatics approach was used to analyze the expression of G9a in breast tissues and its association with the prognosis of the patients with breast cancer. UNC0631, a G9a inhibitor, was used to investigate the effect of G9a on the proliferation of breast cancer cells in vitro. Results The results of immunohistochemical study, real-time PCR and bioinformatics analysis showed that G9a was highly expressed in human breast cancer tissues. G9a was highly expressed in breast invasive ductal carcinoma, and its expression was negatively correlated with age (P<0.05). Her-2-overexpressing breast cancer showed high expressions of G9a, which was positively correlated with the expressions of Her-2, Ki-67 and E-cadherin (P<0.05). Bioinformatics analysis suggested that a high G9a expression was an independent risk factor for poor prognosis of breast cancer. In cultured breast cancer cells, the application of the G9a inhibitor significantly inhibited the cell proliferation. Conclusion G9a is highly expressed in breast cancer tissues to promote the development and progression of breast cancer. A high G9a expression is an independent risk factor for poor prognosis of breast cancer, and G9a may serve as a new target for early diagnosis and treatment of breast cancer.