Cellular ras gene activity is required for full neoplastic transformation by the large tumor antigen of SV40.
To investigate the role of the cellular ras gene product in neoplastic transformation by the SV40 large tumor antigen (SVLT), murine C3H10T1/2 cells were rendered deficient in Ras activity by transfection with inducible or constitutive antisense ras gene constructs or through the introduction of the dominant-negative mutant, ras(asn17). Consistent with previous results, SVLT-induced morphological transformation was unaffected by the down-regulation of c-ras gene product activity. On the other hand, colony formation in soft agar and tumorigenicity in nude mice were drastically reduced in c-Ras-deficient cells. In addition, SVLT expression in C3H10T1/2 cells led to increased c-Ras activity, as determined by an increase in the Ras-bound GTP/GTP + GDP ratio. These results suggest that c-Ras is required for full neoplastic transformation by SVLT.
Raptis
L
L
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada. raptisl@post.queensu.ca
Brownell
H L
HL
Corbley
M J
MJ
Wood
K W
KW
Wang
D
D
Haliotis
T
T
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005347:Fibroblasts; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics; D027384:Oncogene Proteins v-raf; D016372:RNA, Antisense; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D013539:Simian virus 40 / Q000276:immunology*; D014162:Transfection; D018631:ras Proteins / Q000032:analysis / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D016372:RNA, Antisense; D015682:Retroviridae Proteins, Oncogenic; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D027384:Oncogene Proteins v-raf; D018631:ras Proteins