Expression cDNA cloning of a transforming gene encoding the wild-type G alpha 12 gene product.
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 G alpha 12. NIH 3T3 cells transfected with G alpha 12 cDNA grew in soft agar and were tumorigenic in nude mice. There were no apparent mutations in the cloned cDNA in comparison with a G alpha 12 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 G alpha 12 showed a certain degree of dependency on serum factors, and its mitogenic potential was also potently inhibited by suramin treatment.
Chan
A M
AM
Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892.
Fleming
T P
TP
McGovern
E S
ES
Chedid
M
M
Miki
T
T
Aaronson
S A
SA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000502:physiology; D015723:Gene Library; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009857:Oncogenes; D017386:Sequence Homology, Amino Acid; D013498:Suramin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D013498:Suramin; D004247:DNA; D019204:GTP-Binding Proteins