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Chemo-resistance-related genes detected by cDNA microarray

cDNA微阵列检测化疗耐药相关基因

基本信息

批准号：
14571225
负责人：
KUBOTA Tetsuro
金额：
$ 2.56万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571225/
关键词：
cDNA microarray gastric cancer clustering cehmosensitivity MTT assay resistance-related gene mRNA CDNAマイクロアレイ

项目摘要

To identify chemoresistance-related genes of gastric cancer, we utilized cDNA microarray technology. Thirty-five gastric cancer specimens surgically resected at our institute between 1998 and 1999 were studied for quantification of 6,300 gene expression by means of oligonucleotide microarray methods, and the calculated gene expressions were evaluated comparing with chemoresistance of each specimens, which was determined by MTT assay (the tetrazolium-based 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay). Inhibition rates (IR) were determined for cisplatin (DDP), 5-fluorouracil (5-FU), mitomycin C or doxorubicin. IR more than or equal to 60% was regarded as sensitive to each agent, and IR less than 40% defined as resistant. Clustering was successfully completed for DDP, resulting in selection of 23 candidates as DDP resistance-related genes, including vascular permeability factor, 2 membrane transporting subunits, and retinoblastoma-binding protein-1. In addition, fur … More ther selection of the DDP resistance-related genes was performed following to these two criteria ; 1)Expression of its gene can be detected in more than 70% of the resistant tumors. 2)Expression detected in less than 30% of the sensitive tumors. 3)Expression levels in tumors twice that of normal mucosa in more than 50% of specimens. Then, metallothionein-IG and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were identified as candidates of DDP-resistance-related genes. When known resistance-related genes to DDP were analyzed according to the MTT assay result, a family of glutathione-S-transferase and cyclooxygenase-2 genes were also evaluated as resistance-related genes. For 5-FU resistance, expression of dihydropyiimidine dehydrogenase and heparin-binding EGF-like growth factor genes were also suggested to be 5-FU resistance-related genes. The present study demonstrated that oligonucleotide microarrays would be useful in providing further information regarding chemoresistant-factors in cancer. Less

为了筛选胃癌耐药相关基因，我们利用cDNA微阵列技术。应用寡核苷酸芯片技术对1998 ~ 1999年在我所手术切除的35例胃癌标本进行了6,300个基因表达的定量分析，并与MTT法测定的各标本化疗耐药性进行比较（基于四唑鎓的3-（4，5-二甲基噻唑-2基）-2，5-二苯基-溴化四唑鎓测定）。测定顺铂（DDP）、5-氟尿嘧啶（5-FU）、丝裂霉素C或阿霉素的抑制率（IR）。IR ≥ 60%为敏感，IR <40%为耐药。成功完成了DDP的聚类，从而选择了23个候选基因作为DDP耐药相关基因，包括血管通透性因子、2个膜转运亚基和视网膜母细胞瘤结合蛋白-1。此外，Fur ...更多信息根据以下两个标准进行DDP耐药相关基因的筛选：1）在70%以上的耐药肿瘤中可检测到其基因的表达。2)在不到30%的敏感肿瘤中检测到表达。3)在超过50%的标本中，肿瘤中的表达水平是正常粘膜的两倍。金属硫蛋白-IG和肝素结合表皮生长因子样生长因子（HB-EGF）被确定为DDP耐药相关基因的候选基因。当根据MTT试验结果分析已知的DDP耐药相关基因时，谷胱甘肽-S-转移酶和环氧合酶-2基因家族也被评估为耐药相关基因。对于5-FU耐药，二氢嘧啶脱氢酶和肝素结合EGF样生长因子基因的表达也被认为是5-FU耐药相关基因。本研究表明，寡核苷酸芯片将是有用的，在提供进一步的信息，化疗耐药因素在癌症。少