來自哈爾濱醫(yī)科大學(xué),，黑龍江省醫(yī)學(xué)分子生物學(xué)重點實驗室等處的研究人員通過免疫組化等方面的實驗，分析了HIC1和TOB1蛋白的表達和調(diào)控,，識別出了5個LOH亞區(qū)域,，為胃癌研究提供了重要的理論資料和臨床資料。這一研究成果公布在《分子與細(xì)胞》Molecules and cells雜志上,。
領(lǐng)導(dǎo)這一研究的是哈爾濱醫(yī)科大學(xué)副校長傅松濱教授,，其現(xiàn)任遺傳學(xué)教授，博士研究生導(dǎo)師,，醫(yī)學(xué)遺傳學(xué)研究室主任,，哈爾濱醫(yī)科大學(xué)副校長。主要從事“中國不同人群遺傳資源保存及多樣性研究”和“雙微體的結(jié)構(gòu)與功能研究”,。
胃癌是消化系統(tǒng)最常見的惡性腫瘤之一,。胃癌可發(fā)生于任何年齡，但總的趨勢是發(fā)病率隨著年齡的增長而上升,。青年人所患的胃癌,，其惡性程度相對于中老年患者往往更為突出，應(yīng)予以高度重視。由于胃癌在我國極為常見,，危害性大,，有關(guān)研究認(rèn)為其發(fā)病原因與飲食習(xí)慣、遺傳因素,、胃部疾病等有關(guān),。
之前，這一研究小組曾識別了17號染色體上雜合性丟失(loss of heterozygosity,，LOH)的三個重疊區(qū)域——LOH是一種等位基因缺失,，表現(xiàn)為與同一個體正常組織相比，腫瘤組織的一個等位基因消失,。在這一研究的基礎(chǔ),，研究人員通過免疫組化實驗，甲基化特異性PCR（methylation-specific PCR,，MSP）,，以及Western Blot實驗，分析了HIC1和TOB1蛋白的表達和調(diào)控,，并識別出了5個更小的LOH亞區(qū)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個常見事件，而且可能會促進這一疾病的發(fā)展,。這一研究對于胃癌的理論研究和臨床研究具有重要意義,。
這一研究組集中探討胃癌相關(guān)染色體區(qū)域缺失和擴增情況，胃癌相關(guān)基因的突變熱點及其表達變異,，人類原發(fā)胃癌差異表達基因及其功能,，他們曾在對胃癌形成的變化規(guī)律及早期信號的研究中，通過對四種胃癌細(xì)胞系Twist蛋白水平的篩選,，發(fā)現(xiàn)Twist在調(diào)控胃癌侵襲和轉(zhuǎn)移中重要作用,。（生物谷Bioon.com）
生物谷推薦原文出處：
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.
