干扰素／维甲酸联合应用诱导的细胞凋亡相关基因-19、信号转导与转录激活因子3、髓样细胞白血病-1表达与食管鳞癌细胞增殖和凋亡的关系  

Relationship between expression of genes associated with retinoid interferon induced mortality - 19, signal transducer and activators of transcription 3, and myeloid cell leukemia - 1 with proliferation and apoptosls of esophageal squamous carcinoma cells

作　　者：孙淼淼 王建君[2] 张红新[2] 陈奎生 

机构地区：[1]郑州大学附属肿瘤医院病理科,450003 [2]郑州大学第一附属医院病理科暨河南省肿瘤病理重点实验室,450052

出　　处：《中华实验外科杂志》2017年第9期1479-1482,共4页Chinese Journal of Experimental Surgery

基　　金：河南省基础与前沿技术研究计划项目（142300410076、122300413204）

摘　　要：目的探讨细胞凋亡相关基因-19、信号转导与转录激活因子-3（STAT3）、髓样细胞白血病-1（Mcl-1）表达与食管鳞癌细胞增殖和凋亡的关系及其机制。方法 采用免疫组织化学链菌素抗生物素蛋白-过氧化物酶（SP）法分别检测GRIM-19、STAT3、Mcl-1蛋白以及细胞核增殖抗原（Ki-67）在50例食管鳞癌组织、30例癌旁不典型组织以及50例正常食管黏膜组织中的表达；应用原位杂交法分别检测50例食管鳞癌组织、30例癌旁不典型增生和50例正常食管黏膜组织中GRIM-19、STAT3、Mcl-1 mRNA的表达；采用原位缺口末端标记法（TUNEL）方法检测食管鳞癌组织中肿瘤细胞的凋亡。结果 GRIM-19蛋白和mRNA在食管鳞癌组织中阳性率明显低于癌旁不典型增生组织以及正常食管黏膜组织（蛋白：χ2＝12.130，P＝0.000；mRNA： χ2＝11.830, P＝0.000）；信号转导与转录激活因子-3（STAT3）、Mcl-1蛋白和mRNA在食管鳞癌组织中的阳性率明显高于癌旁不典型增生组织以及正常食管黏膜组织（STAT3蛋白：χ2＝4.910，P＝0.000, STAT3 mRNA： χ2＝5.410, P＝0.000; Mcl-1蛋白：χ2＝4.970，P＝0.000, Mcl-1 mRNA： χ2＝5.370, P＝0.000）；GRIM-19蛋白阳性表达组中肿瘤细胞凋亡指数（AI）显著高于阴性表达组（F＝18.355，P＝0.048）；STAT3和Mcl-1蛋白阳性表达组中肿瘤细胞AI显著低于阴性表达组（STAT3蛋白阳性组：F＝19.003，P＝0.036；Mcl-1蛋白阳性组：F＝18.225，P＝0.044）；Ki-67的表达与GRIM-19蛋白、mRNA的表达呈负相关（r＝－0.712，P＝0.040）；与STAT3、Mcl-1蛋白、mRNA的表达均呈正相关（STAT3：r＝0.878，P＝0.039，0.041；Mcl-1：r＝0.653，P＝0.041）。结论GRIM-19低表达、STAT3和Mcl-1高表达可促进食管鳞癌细胞增殖，抑制其凋亡，GRIM-19可能通过下调STAT3表达，并进一步降低Mcl-1表达，从而影响食管鳞癌细胞增殖和凋亡。Objective To investigate the relationship between the expression of genes associated with retinoid interferon induced mortality-19 （GRIM-19）, signal transducer and activators of transcription 3 （STAT3）, and myeloid cell leukemia-1 （Mcl-1） with esophageal squamous carcinoma cells proliferation and apoptosis and the possible mechanism. Methods The protein expression of GRIM-19, STAT3, Mcl-1 and proliferation cell nuclear antigen （Ki-67） in 50 cases of esophageal squamous carcinoma tissues, 30 cases of atypical tissue adjacent to carcinoma and 50 cases of normal esophageal mucosa tissues was detected by immunohistochemical streptavidin avidin-peroxidase （SP） method. The mRNA expression of GRIM-19, STAT3, Mcl-1 and Ki-67 in 50 cases of esophageal squamous carcinoma tissues, 30 cases of atypical tissue adjacent to carcinoma and 50 cases of normal esophageal mucosa tissues was detected by in situ hybridization. TdT-mediated deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） method was applied to examine apoptosis of esophageal squamous carcinoma cells. Results The positive expression rate of GRIM-19 protein and mRNA in esophageal squamous carcinoma tissues was significantly lower than that in atypical hyperplasia tissue adjacent to carcinoma and normal esophageal mucosa （protein： χ2=12.130, P=0.000; mRNA： χ2=11.830, P=0.000）. The positive expression rate of STAT3 and Mcl-1 protein and mRNA in esophageal squamous carcinoma tissues was significantly higher than that in atypical hyperplasia tissue adjacent to carcinoma and normal esophageal mucosa （STAT3 protein： χ2=4.910, P=0.000, STAT3 mRNA： χ2=5.410, P=0.000; Mcl-1 protein： χ2=4.970, P=0.000, Mcl-1 mRNA： χ2=5.370, P=0.000）. The apoptosis of tumor cells in esophageal squamous carcinoma tissues was associated with the positive expression rate of GRIM-19, STAT3 and Mcl-1. The apoptosis index （AI） in the group of GRIM-19 positive expression was higher than that in the group of GRIM-19 negative expression

关 键 词：细胞凋亡相关基因-19 信号转导与转录激活因子-3 髓样细胞白血病-1 食管癌 脱噬作用 

分 类 号：R735.1[医药卫生—肿瘤]