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Expression cloning of anticancer drug-sensitivity-regulatory molecules in gynecologic malignancy

妇科恶性肿瘤抗癌药敏调节分子的表达克隆

基本信息

批准号：
11671642
负责人：
TANAKA Tetsuji
金额：
$ 2.3万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671642/
关键词：
drug-resistance expression cloning differential display

项目摘要

In this study, molecular cloning of anticancer drug-resistance-related genes were performed by using various anticancer drug-resistant subclones we have originally established from gynecological cancer cell lines. Moreover, analyses of regulatory mechanisms of anticancer drug-sensitivity in the drug-resistant sublines we established were also examined.First, we have been applied differential display procedure to RNA extracted from the various drug-resistant subclones. The experiments have not been finished yet. By the differential display method. several candidate genes related to anticancer drug-sensitivity/resistance such as aldehyde dehydrogenase, T-cell leukemia related genes, cytochome C gene and interleukin-13 receptor gene were selected. We are now under investigation of functional analyses of the candidate genes.Although in fact we have found lots of discovery in drug-resistance mechanisms by analyses of the established drug-resistant sublines, we did not have enough time to publish these results on international journals. On more than one hundred of resistant subclone, we analyzed them by cross-resistance to other anticancer drugs, expression of known drug-resistance-related genes (quantitative Taq-Man RT-PCR), immunocytochemistry and flow cytometry. Chromosomal analyses were also examined.We are investigating differential expressions of 1,176 genes in the drug-resistance cancer cells by DNA microarray technology. Together with pharmaceutical company which have developed anticancer drugs, we are searching candidate drugs to recover drug-sensitivity in the drug-resistant cells.

在这项研究中，抗癌药物耐药相关基因的分子克隆进行了使用各种抗癌药物耐药亚克隆，我们最初建立了妇科癌细胞系。此外，我们还建立了耐药亚系抗癌药物敏感性的调节机制的分析进行了检查。首先，我们已经应用差异显示程序从不同的耐药亚系提取的RNA。实验还没有完成。采用差异显示法。筛选出与抗癌药物敏感性/耐药性相关的几个候选基因，如醛脱氢酶、T细胞白血病相关基因、细胞色素C基因和白细胞介素13受体基因。我们目前正在进行候选基因的功能分析，虽然事实上我们已经通过对已建立的耐药亚系的分析发现了许多耐药机制的发现，但我们没有足够的时间将这些结果发表在国际期刊上。对100余株耐药亚克隆进行交叉耐药、已知耐药相关基因表达（Taq-Man RT-PCR）、免疫细胞化学和流式细胞术分析。我们正在利用DNA微阵列技术研究耐药癌细胞中1，176个基因的差异表达。我们与开发抗癌药物的制药公司一起，正在寻找候选药物，以恢复耐药细胞的药物敏感性。