Identification of novel gastric cancer-related genes with transforming activity

具有转化活性的新型胃癌相关基因的鉴定

基本信息

批准号：
11470265
负责人：
YAMAMICHI Keigo
金额：
$ 8.9万
依托单位：
Kansai Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

The present study was directed towards the identification of novel factors involved in the transformation process leading to the formation of gastric cancer. A cDNA library from human gastric cancer cells was constructed using a retrovirus vector. Functional cloning was performed by screening for transformation activity in transduced NIH3T3 cells. A total of 6 cDNA clones were isolated, including one encoding the elongation factor 1α subunit which has already been known to play a role in tumorigenesis. One cDNA (clone 56.2), which was repeatedly isolated during the course of screening, encoded a protein identical to a G-protein-coupled receptor protein, GPR35. In addition, another cDNA clone (72.3) was found to be an alternatively spliced product of the GPR35 gene, whereby an additional 31 amino acids were added to the N-terminus of GPR35. Hence, the proteins encoded by clones 56.2 and 72.3 were designated GPR35a and GPR35b, respectively. RT-PCR experiments revealed that GPR35 gene expression is low or absent in the surrounding non-cancerous regions, while both mRNAs were present in all of the gastric cancers examined. The level of 72.3 encoded mRNA was consistently significantly higher than that of 56.2 encoded mRNA. An expression pattern similar to that observed in gastric cancers was detected in normal intestinal mucosa. Based on the apparent transformation activities of the two GPR35 clones in NIH3T3 cells, and the marked up-regulation of their expression levels in cancer tissues, it is speculated that these two novel isoforms of GPR35 play significant roles during the course of gastric cancer formation.

目前的款项针对转化过程，使用逆转录病毒载体构建了来自人类胃癌细胞的cDNA文库。筛选，编码与GPR35相同的蛋白质，另外，另一个cDNA克隆（72.3）是GPR35基因的基础，从而将31个氨基酸添加到GPR35的N-末端。克隆56.2分别被指定为GPR35a，GPR35B分别在周围的非癌性区域中较低或缺乏，而在所有胃癌中都存在两个mRNA。 56.2编码的mRNA。胃癌的形成。