抑癌基因ING1在大肠癌中的表达与突变(英文)  

Expression and mutation of cancer suppressor gene ING1 in colorectal cancers

作　　者：王自强[1] 周燕虹[1] 蔡志民[1] 余佩武[1] 

机构地区：[1]解放军第三军医大学西南医院普外科,重庆市400038

出　　处：《中国临床康复》2005年第22期262-264,F003,共4页Chinese Journal of Clinical Rehabilitation

摘　　要：背景:抑癌基因ING1高表达可使多种癌细胞发生细胞凋亡,并使其细胞在合成前期细胞周期静止。ING1参与p53的信号传递通路,以一种转录活化因子调节p53的活性。目的:探讨人大肠癌组织中ING1基因表达及突变水平与大肠癌临床病理特征的关系。设计:以病理标本为观察对象的对照实验。单位:解放军第三军医大学西南医院普外科。对象:取自1998-10/1999-10在第三军医大学西南医院住院手术患者切除的大肠癌标本52块,于手术中分别取自距肿瘤边缘10cm正常黏膜及新鲜肿瘤组织。患者男29例,女23例;平均年龄50.28岁。方法:检测52块大肠癌组织标本中ING1mRNA及蛋白的表达情况,DNA单链多态性分析法检测基因突变情况。同时应用免疫组织化学方法检测大肠癌中P53蛋白表达情况。主要观察指标:①ING1mRNA及蛋白在结直肠癌中的表达。②P53在结肠癌中的表达。③聚合酶链反应-SSCP分析ING1基因突变情况。结果:①ING1mRNA在结直肠癌标本表达较正常黏膜明显减弱(0.626±0.382,1.166±0.245,P<0.001)。淋巴结转移阳性组肿瘤组织中ING1表达强度较阴性组中显著下降(0.393±0.243,0.960±0.299,P<0.01)。②P53蛋白表达强度与ING1mRNA表达相对强度呈显著正相关(P<0.01)。③52块标本仅检测到1块存在ING1mRNA基因表达突变。结论:ING1基因可能参与了结直肠癌的发生与发展,其降低使结肠癌患者抑癌基因不能发挥。通过ING1mRNA及蛋白表达的下降而不是基因位点的丢失和突变,提示ING1不像传统的抑癌基因那样主要通过基因位点的丢失和突变来参与癌症的发生,可能存在其他机制参与到ING1基因表达的缺失。BACKGROUND:Overexpression of cancer suppressor gene ING1 may cause apoptosis of many kinds of cancer cells and results in cell cycle arrest in G1 stage.ING1 is involved in p53 signaling pathway and regulates the activity of p53 as a transcription-activating factor. OBJECTIVE:To explore the association of ING1 gene expression and mutation with the clinicpathological features of colorectal cancer. DESIGN:A controlled observation of the pathological samples. SETTING:Department of General Surgery,Southwest Hospital, Third Military Medical University of Chinese PLA. PARTICIPANTS:Totally 52 fresh colorectal cancer samples were obtained from patients hospitalized in the Southwest Hospital,Third Military Medical University of Chinese PLA from October 1998 to October 1999. Normal mucosal tissues were also collected 10 cm from the margin of the tumor during the operation.The patients included 29 male and 23 female patients with an average age of 50.28 years. METHODS:ING1mRNA and protein expressions were detected in the 52 colorectal cancer tissue samples.The ING1 gene mutation was detected by analyzing single-stranded DNA polymorphism.The expression of p53 protein in the colorectal cancer tissue was detected immunohistochemically. MAIN OUTCOME MEASURES: ①ING1 mRNA and protein expressions in the colorectal cancer tissue;②p53 expression in the colorectal cancer tissue;③ING1 gene mutation analyzed by polymerase chain reaction-single-strand conformation polymorphism . RESULTS:①The expression of ING1 mRNA in the colorectal cancer tissue was obviously decreased in comparison with that in the normal mucosa(0.626 ±0.382 vs 1.166±0.245, P< 0.001). The expression of ING1 in the tumor tissue of patients with lymphatic metastasis was significantly lower than that in the tumor tissues from patients without lymphatic metastasis(0.393±0.243 vs 0.960±0.299,P< 0.01).The expression of p53 protein was positively correlated with ING1 mRNA expression(P< 0.01).Only one of the 52 samples was positive for ING1 gene mutation. CONCLUSIO

关 键 词：结直肠肿瘤 逆转录聚合酶链反应 突变 

分 类 号：R73[医药卫生—肿瘤]