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The mutation enhancement in human cell lines by serum factors from pancreatic cancer patients

胰腺癌患者血清因子对人类细胞系的突变增强作用

基本信息

批准号：
09671209
负责人：
YAMAMORI Hideo
金额：
$ 2.05万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671209/
关键词：
pancreatic cancer serum factor K-ras mutation protease 膵臓癌遺伝子

项目摘要

In pancreatic cancer cells base institution mutation is very highly detected. We have reported that sera from pancreatic cancer patients have the ability to enhance the mutation frequency. In the present research effects of the sera on protein and DNA metabolism were studied, in order to clarify mechanism of the enhancement activity. We have already found that human interferon induce the activity of antipain-sensitive proteases in early steps of suppression of the mutation incidence. Thus, fibrinolysis activity was estimated using ^<125>I-fibrin as substrates in cells pretreated with serum factors from pancreatic cancer patients and then irradiated with UV.The factors were obtained by a color-column chromatography method. The fraction sample was obtained which enhance frequencies of ouabain-resistant phenotypic mutation induced by UV.The fraction sample also showed the ability to enhance frequencies of K-ras codon 12 mutation detected by the PCR-based differential dot-blot hybridization analysis. Furthermore the sample enhance the proteases activity induced by UV On the other hand, induction of several genes expression was identified by the RT mRNA differential display method.Therefore, it was suggested that serum factors from pancreatic cancer patients enhance K-ras codon 12 mutation possibly via proteases induction followed by several genes expression.

在胰腺癌细胞中，碱基突变的检测率非常高。我们报道称，胰腺癌患者的血清能够提高突变频率。本研究主要研究血清对蛋白质和DNA代谢的影响，以阐明其增强活性的机制。我们已经发现，人干扰素在抑制突变发生的早期步骤中诱导抗痛敏感蛋白酶的活性。因此，在用来自胰腺癌患者的血清因子预处理然后用UV照射的细胞中使用125 I-纤维蛋白作为底物来估计纤维蛋白溶解活性。通过彩色柱色谱法获得因子。获得的级分样品提高了由UV诱导的哇巴因抗性表型突变的频率。级分样品还显示出提高基于PCR的差异点印迹杂交分析检测到的K-ras密码子12突变频率的能力。此外，样品增强了UV诱导的蛋白酶活性。另一方面，通过RT mRNA差异显示方法鉴定了多个基因表达的诱导。因此，表明来自胰腺癌患者的血清因子可能通过蛋白酶诱导随后几个基因的表达来增强K-ras密码子12突变。