C-Raf-1 protein kinase is not essential for Ras transformation of mouse embryo fibroblasts.
Transfection of primary cells with mutated oncogenic ras plus a cooperating oncogene such as myc results in the acquisition of the transformed cell phenotype. The pathways downstream of Ras that are required for transformation are an active topic of research. The Raf-MEKK-MAP kinase pathway is triggered by activation of Ras and thought to be important in Ras transformation of rodent fibroblasts. To further explore the involvement of this pathway, fibroblasts from homozygous knock out c-Raf-1 mouse embryos (20 KO) and wild-type c-Raf-1 mouse embryos (16 WT) were transfected with H-ras and myc(v). The resulting cell line derived from the knock out cells grew slower both in tissue culture and had a longer latency period as tumors than the transformed cell line from the wild-type cells. Both cell lines were however able to form tumors in nude mice. These results suggest that c-Raf-1 is not required for Ras transformation in this system.
Gupta
Anjali K
AK
Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072, USA. gupta@xrt.upenn.edu
Bernhard
Eric J
EJ
Bakanauskas
Vincent J
VJ
Cerniglia
George J
GJ
Muschel
Ruth J
RJ
McKenna
Gillies
G
D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006720:Homozygote; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D019908:Proto-Oncogene Proteins c-raf / Q000172:deficiency / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation
D019908:Proto-Oncogene Proteins c-raf; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)