Oncogene：发现抑制胃癌的重要基因

       国际癌症研究权威刊物Oncogene（癌基因）在线新近发表了上海交通大学医学院附属瑞金医院外科胃癌研究课题组的此项最新研究成果。

       该课题组研究人员经过近5年潜心研究发现，位于5号染色体短臂上的同源盒基因IRX1的活性丢失可导致胃癌细胞增殖与侵袭能力增加。研究人员发现，通过转基因技术将该基因导入胃癌细胞，使IRX1基因活性恢复后，无论是体外培养的胃癌细胞，还是小鼠活体内的肿瘤细胞，其恶性增殖与侵袭能力均受到明显抑制。

       专家指出，该研究不仅首次提出IRX1基因在胃癌发生发展中的抑癌基因作用，还发现了另外一个重要现象，即：不但胃癌组织中可以检测到IRX1基因启动子的高甲基化，在胃癌患者的外周血游离DNA中也可以检测到IRX1基因的高甲基化。专家指出，这为今后将IRX1基因甲基化分析作为胃癌诊断中的新型分子标志物提供了重要线索。

       院方有关人士告诉记者，该课题是上海瑞金医院外科胃癌研究课题组的原创性研究，近几年来得到国家自然科学基金的连续资助，同时得到国家科技部高技术发展计划863重大项目以及上海市科委的支持。

       生物谷推荐原文出处：

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.