Oncogenicity of human N-ras oncogene and proto-oncogene introduced into retroviral vectors

Journal Article · Fri Sep 01 04:00:00 EDT 1989 · Journal of Virology; (USA)

OSTI ID:7194722

Souyri, M; Vigon, I; Charon, M; Tambourin, P ^[1]

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1. Hopital Cochin, Paris (France)

The N-ras gene is the only member of the ras family which has never been naturally transduced into a retrovirus. In order to study the in vitro and in vivo oncogenicity of N-ras and to compare its pathogenicity to that of H-ras, the authors have inserted an activated or a normal form of human N-ras cDNA into a slightly modified Harvey murine sarcoma virus-derived vector in which the H-ras p21 coding region had been deleted. The resulting constructions were transfected into NIH 3T3 cells. The activated N-ras-containing construct (HSN) induced 10{sup 4} foci per {mu}g of DNA and was found to be as transforming as H-ras was. After infection of the transfected cells by either the ecotropic Moloney murine leukemia virus or the amphotropic 4070A helper viruses, rescued transforming viruses were injected into newborn mice. Both pseudotypes of HSN virus containing activated N-ras induced the typical Harvey disease with similar latency. However, they found that the virus which contained normal N-ras p21 (HSn) was also pathogenic and induced splenomegaly, lymphadenopathies, and sarcoma in mice after a latency of 3 to 7 weeks. In addition, Moloney murine leukemia virus pseudotypes of N-ras caused neurological disorders in 30% of the infected animals. These results differed markedly from those of previous experiments in which the authors had inserted the activated form of N-ras in the pSV(X) vector: the resulting SVN-ras virus was transforming on NIH 3T3 cells but was poorly oncogenic in vivo. Altogether, these data demonstrated unequivocally that N-ras is potentially as oncogenic as H-ras and that such oncogenic effect could depend on the vector environment.

• OSTI ID: 7194722
• Journal Information: Journal of Virology; (USA), Journal Name: Journal of Virology; (USA) Vol. 63:9; ISSN 0022-538X; ISSN JOVIA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DNA HYBRIDIZATION
DNA SEQUENCING
FIBROBLASTS
GENES
HYBRIDIZATION
INFECTIOUS DISEASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MICE
MICROORGANISMS
MOLECULAR BIOLOGY
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ONCOGENES
ONCOGENIC VIRUSES
ORGANIC COMPOUNDS
PARASITES
PATHOGENESIS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RECOMBINANT DNA
RODENTS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
VIRAL DISEASES
VIRUSES