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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: High expression of the tumor suppressor gene ING1 can induce apoptosis of many kinds of cancer cells and make their cells quiescent in the early stage of the cell cycle. ING1 is involved in the p53 signaling pathway and regulates p53 activity with a transcriptional activator. Objective: To investigate the relationship between the expression of ING1 gene in human colorectal carcinoma and the clinicopathological features of colorectal cancer. Design: a control study of pathological specimens for the observation object. Unit: General Surgery, Southwest Hospital, Third Military Medical University. PARTICIPANTS: Fifty-two specimens of colorectal cancer resected from hospitalized patients in Southwest Hospital of the Third Military Medical University from October 1998 to October 1999 were collected from normal mucosa of 10 cm and fresh tumor tissue respectively from the edge of tumor. There were 29 males and 23 females with an average age of 50.28 years old. Methods: The expression of ING1 mRNA and protein in 52 colorectal cancer tissues was detected by DNA single-strand polymorphism analysis. Immunohistochemistry was used to detect the expression of P53 protein in colorectal cancer. MAIN OUTCOME MEASURES: ①The expression ofING1 mRNA and protein in colorectal cancer. ② p53 expression in colon cancer. ③ polymerase chain reaction-SSCP analysis of ING1 gene mutations. Results: ① The expression ofING1 mRNA in colorectal cancer specimens was significantly weaker than that in normal mucosa (0.626 ± 0.382, 1.166 ± 0.245, P <0.001). The expression of ING1 in lymph node positive group was significantly lower than that in negative group (0.393 ± 0.243,0.960 ± 0.299, P <0.01). ②P53 protein expression intensity and the relative intensity of ING1 mRNA expression was positively correlated (P <0.01). ③ Only one piece of ING1mRNA gene expression mutation was detected in 52 samples. Conclusion: ING1 gene may be involved in the occurrence and development of colorectal cancer, and its decrease can make tumor suppressor gene in colon cancer patients unable to play. The decrease of ING1mRNA and protein expression, but not the loss and mutation of the gene locus suggest that ING1 is not involved in the development of cancer mainly through the loss and mutation of the gene locus like the traditional tumor suppressor genes. There may be other mechanisms involved in the ING1 gene Lack of expression.