EXPRESSION CDNA CLONING OF A TRANSFORMING GENE ENCODING THE WILD-TYPE G-ALPHA-12 GENE-PRODUCT
EXPRESSION CDNA CLONING OF A TRANSFORMING GENE ENCODING THE WILD-TYPE G-ALPHA-12 GENE-PRODUCT
复制标题
DOI：
10.1128/mcb.13.2.762
复制
发表时间：
1993-02-01
影响因子：
5.3
通讯作者：
AARONSON, SA
中科院分区：
文献类型：
--
作者：
CHAN, AML;FLEMING, TP;AARONSON, SA
使用表达cDNA克隆的方法，我们研究了人类肿瘤细胞系的新癌基因，可能逃避检测通过常规技术。我们分离了一种转化NIH 3T3小鼠成纤维细胞的转化序列。DNA序列分析确定该基因是最近克隆的小鼠GTP结合蛋白Galpha12 α亚基的人类同源物。转染Galpha12 cDNA的NIH 3T3细胞在软琼脂中生长，并在裸鼠体内具有致瘤性。与从正常人上皮细胞文库中分离的Galpha12 cDNA克隆相比，在克隆的cDNA中没有明显的突变，这意味着仅过表达就足以引起NIH 3T3细胞转化。所观察到的Galpha12介导的改变的生长特性表现出一定程度的依赖于血清因子，其促有丝分裂的潜力也有力地抑制苏拉明治疗。
Using an expression cDNA cloning approach, we examined human tumor cell lines for novel oncogenes that might evade detection by conventional techniques. We isolated a transforming sequence that was highly efficient in transforming NIH 3T3 mouse fibroblasts. DNA sequence analysis identified the gene as the human homolog of a recently cloned alpha subunit of mouse GTP-binding protein Galpha12. NIH 3T3 cells transfected with Galpha12 cDNA grew in soft apr and were tumorigenic in nude mice. There were no apparent mutations in the cloned cDNA in comparison with a Galpha12 cDNA clone isolated from a normal human epithelial cell library, implying that overexpression alone was sufficient to cause NIH 3T3 cell transformation. The observed altered growth properties mediated by Galpha12 showed a certain degree of dependency on serum factors, and its mitogenic potential was also potently inhibited by suramin treatment.