Oncogenic potential of BRAF versus RAS.
Mutations in the ERK pathway occur in approximately one-third of all human cancers and most often involve production of mutant RAS or BRAF. Several studies, including our own, have shown that mutations in the BRAF and RAS genes are generally mutually exclusive. This study was performed to determine the relative oncogenic potential of the BRAF and RAS oncogenes. BRAF(V600E)-, H-RAS(G12V)-, and N-RAS(Q61R)-transfected mouse embryonic fibroblasts (MEFs) that lack p53 (p53(-/-)) or contain mutations at codon 172 (p53(R172H) and p53(R172P)) were able to induce morphologically transformed foci in p53(-/-) and p53(R172H) MEFs but not in p53(R172P) MEFs. Interestingly, BRAF(V600E) was less potent than mutant H-RAS(G12V) or N-RAS(Q61R) was in cooperating with mutant p53 as the numbers and sizes of foci induced by BRAF(V600E) were significantly lower and smaller. In vitro growth characteristics and anchorage-independent growth of transfected MEFs corroborated the transformed phenotype, and in vivo tumorigenesis confirmed the results. These results indicate that mutant BRAF(V600E) is weakly oncogenic compared with mutant RAS and that they both cooperate with p53(-/-) and p53(R172H) but not with p53(R172P) in oncogenic transformation.
Benjamin
Cara L
CL
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Ananthaswamy
Honnavara N
HN
D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016158:Genes, p53 / Q000502:physiology; D011905:Genes, ras / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D009374:Neoplasms, Experimental / Q000209:etiology* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D012333:RNA, Messenger; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf