来自哈尔滨医科大学,黑龙江省医学分子生物学重点实验室等处的研究人员通过免疫组化等方面的实验,分析了HIC1和TOB1蛋白的表达和调控,识别出了5个LOH亚区域,为胃癌研究提供了重要的理论资料和临床资料。这一研究成果公布在《分子与细胞》Molecules and cells杂志上。
领导这一研究的是哈尔滨医科大学副校长傅松滨教授,其现任遗传学教授,博士研究生导师,医学遗传学研究室主任,哈尔滨医科大学副校长。主要从事“中国不同人群遗传资源保存及多样性研究”和“双微体的结构与功能研究”。
胃癌是消化系统最常见的恶性肿瘤之一。胃癌可发生于任何年龄,但总的趋势是发病率随着年龄的增长而上升。青年人所患的胃癌,其恶性程度相对于中老年患者往往更为突出,应予以高度重视。由于胃癌在我国极为常见,危害性大,有关研究认为其发病原因与饮食习惯、遗传因素、胃部疾病等有关。
之前,这一研究小组曾识别了17号染色体上杂合性丢失(loss of heterozygosity,LOH)的三个重叠区域——LOH是一种等位基因缺失,表现为与同一个体正常组织相比,肿瘤组织的一个等位基因消失。在这一研究的基础,研究人员通过免疫组化实验,甲基化特异性PCR(methylation-specific PCR,MSP),以及Western Blot实验,分析了HIC1和TOB1蛋白的表达和调控,并识别出了5个更小的LOH亚区域:SR1–SR5 (0.54 - 3.42 cM)。
研究表明HIC1和TOB1蛋白沉默是胃癌中的一个常见事件,而且可能会促进这一疾病的发展。这一研究对于胃癌的理论研究和临床研究具有重要意义。
这一研究组集中探讨胃癌相关染色体区域缺失和扩增情况,胃癌相关基因的突变热点及其表达变异,人类原发胃癌差异表达基因及其功能,他们曾在对胃癌形成的变化规律及早期信号的研究中,通过对四种胃癌细胞系Twist蛋白水平的筛选,发现Twist在调控胃癌侵袭和转移中重要作用。(生物谷Bioon.com)
生物谷推荐原文出处:
Molecules and cells DOI: 10.1007/s10059-011-2316-4
Identification of novel subregions of LOH in gastric cancer and analysis of the HIC1 and TOB1 tumor suppressor genes in these subregions.
Yu Jingcui J,Liu Peng P,Cui Xiaobo X,Sui Yu Y,Ji Guohua G,Guan Rongwei R,Sun Donglin D,Ji Wei W,Liu Fangli F,Liu An A,Zhao Yuzhen Y,Yu Yang Y,Jin Yan Y,Bai Jing J,Geng Jingshu J,Xue Yingwei Y,Qi Jiping J,Lee Ki-Young KY,Fu Songbin S,
Previously, we identified 3 overlapping regions showing loss of heterozygosity (LOH, R(1)-R(3) from 11 to 30 cM) on chromosome 17 in 45 primary gastric cancers (GCs). The data indicated the presence of tumor suppressor genes (TSGs) on chromosome 17 involved in GC. Among the putative TSGs in these regions, HIC1 (in SR(1)) and TOB1 (in SR(3)) remain to be examined in GC. By immunohistochemistry (IHC), methylation-specific PCR (MSP) and western blot, we evaluated the expression and regulation status for HIC1 and TOB1 protein in GC. We narrowed down the deletion intervals on chromosome 17 and defined five smaller LOH subregions, SR(1)-SR(5) (0.54 to 3.42 cM), in GC. We found that HIC1 had downregulated expression in 86% (91/106) and was methylated in 87% (26/30) of primary GCs. Of the primary GCs showing downregulation of HIC1 protein, 75% (18/24) had methylated HIC1 gene. TOB1 was either absent or expressed at reduced levels in 75% (73/97) of the GC samples. In addition, a general reduction was found in total and the ratio of unphosphorylated to phosphorylated TOB1 protein levels in the differentiated GC cell lines. Further analysis revealed significant simultaneous downregulation of both HIC1 and TOB1 protein in GC tissue microarray samples (67%, 52/78) and in primary GCs (65%, 11/17). These results indicate that silencing of HIC1 and TOB1 expression is a common occurrence in GC and may contribute to the development and progression of the disease.