Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Hollander, MC; Balogh, AR; Liwanag, J; Han, W; Linnoila, RI; Anver, MR; Dennis, PA

Published Date

  • August 2008

Published In

Volume / Issue

  • 10 / 8

Start / End Page

  • 866 - 872

PubMed ID

  • 18683321

Pubmed Central ID

  • PMC2504769

Electronic International Standard Serial Number (EISSN)

  • 1476-5586

Digital Object Identifier (DOI)

  • 10.1593/neo.08406


  • eng

Conference Location

  • United States