Wildtype Kras2 can inhibit lung carcinogenesis in mice. Nat Genet 2001 Sep;29(1):25-33
Date
08/31/2001Pubmed ID
11528387DOI
10.1038/ng721Scopus ID
2-s2.0-17944369909 (requires institutional sign-in at Scopus site) 265 CitationsAbstract
Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression.
Author List
Zhang Z, Wang Y, Vikis HG, Johnson L, Liu G, Li J, Anderson MW, Sills RC, Hong HL, Devereux TR, Jacks T, Guan KL, You MMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Carcinogens
Cell Division
Cell Transformation, Neoplastic
Chromosome Mapping
DNA Primers
Heterozygote
Loss of Heterozygosity
Lung Neoplasms
Mice
Proto-Oncogene Proteins
Proto-Oncogene Proteins p21(ras)
ras Proteins
