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Alteration of expression profiling related the biological characteristics of renal cell carcinoma using cDNA microarray.

使用 cDNA 微阵列表达谱的改变与肾细胞癌的生物学特征相关。

基本信息

批准号：
13671633
负责人：
SHIMAZUI Toru
金额：
$ 2.43万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

[Purpose] To evaluate the genomic background affecting clinical characteristics like metastasis, or response to treatment, we analyzed gene expression profiles of the renal cell carcinomas (RCCs) by microarray technology consisting of 4000 human cDNA clones using SKRC cell lines. Results consists of following 2 sections.[Results] (1) To investigate the metastasis related characteristics, We compared gene expression profiles between RCC cell lines originated from primary or metastasis lesions with the normal renal proximal tubular cell line(RPTEC) as a control. The clustering with the selected 62 genes revealed similarity of profiling pattern between SKRC-17 and SKRC-29 cells which were derived from the metastatic lesion. Another line from metastatic lesion, SKRC-52, whose morphology showed unique spindle shape, had different pattern of expression profiling from the other cell lines. We found several genes up-regulated in the cell lines from the metastatic lesion. Unique profiling patte … More rn on gene expression clearly correlated to cell morphology and metastatic potential and these profiling might contribute to identify the genes involved in clinical characteristics of RCC. (2) Because response rate of interferon-alpha (IFN-a) against RCC is low, prediction of good candidates of IFN-a is required in terms of tailor-made treatment for patients with RCC. Six SKRC cell lines were selected as IFN-a-sensitive (SKRC-1, 14, 29, 59) or resistant (33, 52) cell line by means of MTT assay with addition of 1,000 to 10,000 IU/ml of IFN-a. Alteration of gene expression that differs between sensitive and resistant cell lines were confirmed using RT-PCR and Northern blot. Based on the alteration of expression between SKRC series and RPTEC, 1,401 genes were eventually selected. According to clustering analysis with these 1,401 genes, 6 cell lines could be divided into two groups, which were concordant with the sensitivity against IFN-a. In addition, remarkable alteration of gene expression between sensitive and resistant cell lines were observed in 10 genes, e.g. interferon regulatory factor 4. Microarray analysis provided a useful information concerning sensitivity of IFN-a in RCC cell lines. This clustering and/or expression pattern of selected gene set might be available to select patients who is IFN-a-responder. Less

【目的】应用基因芯片技术分析肾细胞癌（RCC）的基因表达谱，以SKRC细胞为研究对象，分析肾癌细胞的基因表达谱。结果包括以下2个部分。[结果]（1）比较原发灶和转移灶来源的肾癌细胞系与正常肾近端小管细胞系（RPTEC）的基因表达谱，探讨肾癌转移相关特征。与选择的62个基因的聚类揭示了源自转移病灶的SKRC-17和SKRC-29细胞之间的谱模式的相似性。另一个来自转移性病变的细胞系SKRC-52，其形态显示独特的纺锤形，具有与其他细胞系不同的表达谱模式。我们在转移灶的细胞系中发现了几个上调的基因。独特的轮廓模式 ...更多信息 rn对基因表达的影响与细胞形态和转移潜力明显相关，这些分析可能有助于识别与RCC临床特征相关的基因。(2)由于干扰素-α（IFN-α）对RCC的应答率较低，因此在为RCC患者量身定制治疗方面需要预测良好的IFN-α候选物。通过添加1，000至10，000 IU/ml IFN-α的MTT测定法，选择六种SKRC细胞系作为IFN-α敏感性（SKRC-1、14、29、59）或抗性（33、52）细胞系。用RT-PCR和北方杂交证实了敏感细胞系和耐药细胞系之间基因表达的差异。基于SKRC系列和RPTEC之间表达的改变，最终选择了1，401个基因。对这1,401个基因进行聚类分析，将6株细胞分为两类，这与IFN-α敏感性相一致。此外，在10个基因中观察到敏感细胞系和耐药细胞系之间的基因表达的显著改变，例如干扰素调节因子4。基因芯片分析提供了一个有用的信息，在RCC细胞系IFN-α的敏感性。所选基因集的这种聚类和/或表达模式可用于选择IFN-α应答者的患者。少