胰岛素样生长因子Ⅱ基因印迹丢失在结直肠腺瘤中的意义  

Loss of Imprinting of Insulin-like Growth Factor Ⅱ and its Significance in Colorectal Adenoma

作　　者：蔡军[1] 张亚历[1] 付祥胜[1] 周永柏[1] 

机构地区：[1]南方医科大学南方医院消化内科,510515

出　　处：《胃肠病学》2009年第3期141-145,共5页Chinese Journal of Gastroenterology

摘　　要：背景：胰岛素样生长因子Ⅱ（IGF-Ⅱ）可促进多种细胞增殖，抑制细胞凋亡，其表达受基因印迹调控,IGF-Ⅱ基因印迹丢失（LOI）与多种肿瘤的发生相关。目前较少见IGF-Ⅱ与结直肠腺瘤关系的研究报道。目的：分析结直肠腺瘤中IGF-Ⅱ的表达及其基因印迹状态，初步探讨两者在结直肠腺瘤发生、发展中的作用。方法：以免疫组化方法检测14例正常结直肠黏膜、12例增生性息肉和53例结直肠腺瘤组织中IGF-Ⅱ的表达，以聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）方法分析IGF-Ⅱ基因印迹状态。结果：IGF—Ⅱ的表达主要定位于细胞质，其表达在正常结直肠黏膜、增生性息肉和腺瘤组织中逐级递增（P＜0．05）。正常黏膜、增生性息肉和腺瘤组织的IGF—Ⅱ杂合子基因型比例分别为42．9％、41．7％和60．4％。杂合子标本中，腺瘤组织的IGF-ⅡLOI发生率显著高于正常黏膜和增生性息肉（68．8％对16．7％和20．0％，P＜0．05）。结论：IGF-Ⅱ LOI可能是导致IGF—Ⅱ蛋白表达增加，促进结直肠腺瘤发生以及向腺癌演变的重要机制。Background：Insulin-like growth factor Ⅱ （IGF-Ⅱ） promotes cell proliferation and inhibits cell apoptosis. The expression of IGF- Ⅱ is controlled by gene imprinting, and loss of imprinting （LOI） of IGF-Ⅱ has been found in some types of cancer. At present, there are few studies on the relationship between IGF-Ⅱ and colorectal adenoma. Aims： To appraise the expression of IGF-Ⅱ and the imprinting status of IGF-Ⅱ gene in colorectal adenoma, and to explore their effects on the development and progression of colorectal adenoma. Methods： Immunohistochemistry was used to determine the expression of IGF-Ⅱ in 14 normal colorectal mucosal tissues, 12 hyperplastic polyps and 53 colorectal adenomas. The imprinting status of IGF-Ⅱ was detected by polymerase chain reaction （PCR）-restriction fragment length polymorphism （RFLP） analysis. Results： IGF-Ⅱ expression was localized predominantly in the cytoplasm, which increased gradually from normal colorectal mucosa, hyperplastic polyp to adenomatous tissues （P〈0.05）. The positivity rate of IGF- Ⅱ DNA heterozygote was 60.4% in colorectal adenoma, 41.7% and 42.9% in hyperplastic polyps and normal mucosal tissues, respectively. In specimens of IGF-Ⅱ DNA heterozygote, the positivity rate of LOI of IGF-Ⅱ was significantly higher in colorectal adenoma than that in normal mucosal tissues and hyperplastic polyps （68.8% vs. 16.7% and 20.0%, P〈0.05）. Conclusions： LOI of IGF-Ⅱ may cause the increase of IGF-Ⅱ expression, thereby promotes the development of colorectal adenoma and the progression to adenocarcinoma.

关 键 词：胰岛素样生长因子Ⅱ 结直肠肿瘤 腺瘤 基因组印迹 多态性 限制性片段长度 

分 类 号：R735.7[医药卫生—肿瘤] R735.35[医药卫生—临床医学]