上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院專家首次發(fā)現(xiàn)了5號(hào)染色體短臂上的同源盒基因IRX1對(duì)抑制胃癌細(xì)胞具有重要作用,。研究人員表示,，此項(xiàng)研究或成為胃癌診斷新型分子標(biāo)志物的重要線索。
國(guó)際癌癥研究權(quán)威刊物Oncogene（癌基因）在線新近發(fā)表了上海交通大學(xué)醫(yī)學(xué)院附屬瑞金醫(yī)院外科胃癌研究課題組的此項(xiàng)最新研究成果,。
該課題組研究人員經(jīng)過近5年潛心研究發(fā)現(xiàn),，位于5號(hào)染色體短臂上的同源盒基因IRX1的活性丟失可導(dǎo)致胃癌細(xì)胞增殖與侵襲能力增加。研究人員發(fā)現(xiàn),，通過轉(zhuǎn)基因技術(shù)將該基因?qū)胛赴┘?xì)胞,，使IRX1基因活性恢復(fù)后，無論是體外培養(yǎng)的胃癌細(xì)胞,，還是小鼠活體內(nèi)的腫瘤細(xì)胞,，其惡性增殖與侵襲能力均受到明顯抑制,。
專家指出，該研究不僅首次提出IRX1基因在胃癌發(fā)生發(fā)展中的抑癌基因作用,，還發(fā)現(xiàn)了另外一個(gè)重要現(xiàn)象,，即：不但胃癌組織中可以檢測(cè)到IRX1基因啟動(dòng)子的高甲基化，在胃癌患者的外周血游離DNA中也可以檢測(cè)到IRX1基因的高甲基化,。專家指出,，這為今后將IRX1基因甲基化分析作為胃癌診斷中的新型分子標(biāo)志物提供了重要線索。
院方有關(guān)人士告訴記者,，該課題是上海瑞金醫(yī)院外科胃癌研究課題組的原創(chuàng)性研究,，近幾年來得到國(guó)家自然科學(xué)基金的連續(xù)資助,，同時(shí)得到國(guó)家科技部高技術(shù)發(fā)展計(jì)劃863重大項(xiàng)目以及上海市科委的支持,。(生物谷Bioon.com)
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生物谷推薦原文出處：
Oncogene doi:10.1038/onc.2010.143
Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma
X Guo, W Liu, Y Pan, P Ni, J Ji, L Guo, J Zhang, J Wu, J Jiang, X Chen, Q Cai, J Li, J Zhang, Q Gu, B Liu, Z Zhu and Y Yu
The IRX1 tumor suppressor gene is located on 5p15.33, a cancer susceptibility locus. Loss of heterozygosity of 5p15.33 in gastric cancer was identified in our previous work. In this study, we analyzed the molecular features and function of IRX1. We found that IRX1 expression was lost or reduced in gastric cancer. However, no mutations were identified in IRX1-encoding regions. IRX1 transcription was suppressed by hypermethylation, and the expression of IRX1 mRNA was partially restored in gastric cancer cells after 5-Aza-dC treatment. Restoring IRX1 expression in SGC-7901 and NCI-N87 gastric cancer cells inhibited growth, invasion and tumorigenesis in vitro and in vivo. We identified a number of target genes by global microarray analysis after IRX1 transfection combined with real-time PCR and chromatin immunoprecipitation assay. BDKRB2, an angiogenesis-related gene, HIST2H2BE and FGF7, cell proliferation and invasion-related genes, were identified as direct IRX1 target genes. The hypermethylation of IRX1 was not only detected in primary gastric cancer tissues but also in the peripheral blood of gastric cancer patients, suggesting IRX1 could potentially serve as a biomarker for gastric cancer.
