人类抑癌基因beclin 1在胃癌和直结肠癌中表达下调的研究(英文)  

The Expression of Human Tumor Suppressor Gene beclin 1 is Down-regulated in Gastric and Colorectal Cancer

作　　者：李子东[1] 陈波[2] 武一清[1] 金峰[2] 夏永静[1] 刘湘军[1] 

机构地区：[1]清华大学医学院生物信息研究所,清华大学生物科学与技术系,生物信息学教育部重点实验室,北京100084 [2]中国医科大学附属第一医院肿瘤外科,沈阳110001

出　　处：《生物化学与生物物理进展》2008年第11期1282-1290,共9页Progress In Biochemistry and Biophysics

基　　金：grants from Tsinghua-Yue-Yuen Medical Sciences Fund, Foundation for the Mainstay Talents of Tsinghua University(20240000530);The National Natural Science Foundation of China (30670851);Wu Shunde Medical Science Research Fund and the Key Project of Chinese Ministry of Education (03180)~~

摘　　要：人类抑癌基因beclin 1通过自噬作用调节细胞生长,但在胃癌和直结肠癌中其表达水平和调控机制仍不清楚.通过检测胃癌和直结肠肿瘤组织中beclin 1基因的表达水平,及DNA异常甲基化和杂合子缺失对其表达的影响,发现与癌旁组织相比,35%的胃癌标本和30%的直结肠癌标本中beclin 1基因表达显著下调.同时发现,beclin 1基因5′端存在一高密度CpG岛,在胃癌和直结肠癌中beclin 1的启动子区域和第二个内含子区域存在甲基化,而杂合子缺失仅在胃癌中发生.这些发现表明beclin 1基因的异常甲基化和杂合子缺失对其在胃癌和直结肠癌中的表达起调控作用.Human tumor suppressor gene beclin 1 regulates cell growth through autophagy. The mRNA expression of beclin 1 was reported to be down-regulated in breast cancer with high frequency of loss of heterozygosity （LOH）. However, there was no report about the expression levels or the regulatory mechanisms of beclin I in gastric and colorectal cancer. Both the mRNA and protein expression levels ofbeclin I was detected in the tissues of gastric and colorectal cancers, as well as the aberrant DNA methylation and LOH related to the expression of beclin 1. By comparing with normal tissues adjacent to the tissue of these tumors, it was found that beclin 1 mRNA expression levels were significantly decreased in gastric tumor tissue. Furtherly by explorating the 5＇ region of beclin 1 gene sequence, a large and dense CpG island was discovered and meanwhile methylations in the promoter and the intron 2 regions of beclin 1 were found in both gastric and colorectal tumors. And LOH was found in gastric tumors. These findings suggested that aberrant DNA methylation, as well as LOH, were involved in the regulation ofbeclin 1 expression in gastric and colorectal cancer.

关 键 词：becli 1 DNA甲基化 杂合子缺失 胃癌 直结肠癌 转录调控 

分 类 号：Q75[生物学—分子生物学] Q78