Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice.
Pten is a negative regulator of the Akt pathway, and its inactivation is believed to be an etiological factor in many tumor types. Pten+/- mice are susceptible to a variety of spontaneous tumor types, depending on strain background. Pten+/- mice, in lung tumor-sensitive and -resistant background strains, were treated with a tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to determine whether allelic Pten deletion can cooperate with NNK in carcinogenesis in lung or other tissues. In lung tumor-resistant C57BL/6 Pten+/- or +/+ mice, NNK treatment did not lead to any lung tumors and did not increase the incidence or severity of tumors previously reported for this strain. In contrast, in a lung tumor-susceptible pseudo-A/J strain, there was a dose-dependent increase in lung tumor size in Pten+/- compared with +/+ mice, although there was no increase in multiplicity. No other tumor types were observed in pseudo-A/J Pten+/- mice regardless of NNK treatment. Lung tumors from these Pten+/- mice had K-ras mutations, retained Pten expression and had similar Akt pathway activation as lung tumors from +/+ mice. Therefore, deletion of a single copy of Pten does not substantially add to the lung tumor phenotype conferred by mutation of K-ras by NNK, and there is likely no selective advantage for loss of the second Pten allele in lung tumor initiation.
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Related Subject Headings
- Species Specificity
- Proto-Oncogene Proteins c-akt
- Phenotype
- PTEN Phosphohydrolase
- Oncology & Carcinogenesis
- Nitrosamines
- Mutation
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice, Inbred A
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Species Specificity
- Proto-Oncogene Proteins c-akt
- Phenotype
- PTEN Phosphohydrolase
- Oncology & Carcinogenesis
- Nitrosamines
- Mutation
- Mice, Transgenic
- Mice, Inbred C57BL
- Mice, Inbred A