A mutant alpha subunit of Gi2 induces neoplastic transformation of Rat-1 cells.
In a recently discovered class of oncogenes, GTPase-inhibiting mutations constitutively activate alpha subunits of signal-transducing guanine nucleotide-binding proteins (G proteins). Somatic mutations in a subclass of endocrine tumors are found in the arginine-179 codon of the alpha subunit of Gi2 (alpha i2), creating the putative gip2 oncogene. We have tested the ability of gip2 to mediate neoplastic transformation of Rat-1 and NIH 3T3 fibroblasts in tissue culture. Expression of a mutant alpha i2 cDNA encoding cysteine in place of arginine-179 (alpha i2-R179C) caused Rat-1 cells to grow to a higher density in monolayer culture, to lose anchorage dependence, and to form tumors when injected subcutaneously into nude mice. In contrast, expression of alpha i2-R179C failed to alter growth or tumorigenicity of NIH 3T3 cells. We conclude that gip2 is an oncogene, by the criterion that it induces neoplastic transformation of Rat-1 cells. Failure of gip2 to transform NIH 3T3 cells is in keeping with clinical indications that gip2 is a tissue-selective oncogene.
Pace
A M
AM
Department of Pharmacology, University of California, San Francisco 94143.
Wong
Y H
YH
Bourne
H R
HR
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D000242:Cyclic AMP / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011905:Genes, ras; D046911:Macromolecular Substances; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D009857:Oncogenes; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D014183:Transplantation, Heterologous
D046911:Macromolecular Substances; D011994:Recombinant Proteins; D000242:Cyclic AMP; D019204:GTP-Binding Proteins