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

Mary Christine Hollander, Andria R. Balogh, Jaminelli Liwanag, Wei Han, Ritva Ilona Linnoila, Miriam R. Anver, Phillip A. Dennis

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)866-872
Number of pages7
JournalNeoplasia
Volume10
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

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Carcinogenesis
Lung
Neoplasms
Mutation
Carcinogens
Tobacco
Alleles
Phenotype
Incidence

ASJC Scopus subject areas

  • Cancer Research

Cite this

Hollander, M. C., Balogh, A. R., Liwanag, J., Han, W., Linnoila, R. I., Anver, M. R., & Dennis, P. A. (2008). Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice. Neoplasia, 10(8), 866-872. https://doi.org/10.1593/neo.08406

Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice. / Hollander, Mary Christine; Balogh, Andria R.; Liwanag, Jaminelli; Han, Wei; Linnoila, Ritva Ilona; Anver, Miriam R.; Dennis, Phillip A.

In: Neoplasia, Vol. 10, No. 8, 08.2008, p. 866-872.

Research output: Contribution to journalArticle

Hollander, MC, Balogh, AR, Liwanag, J, Han, W, Linnoila, RI, Anver, MR & Dennis, PA 2008, 'Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice', Neoplasia, vol. 10, no. 8, pp. 866-872. https://doi.org/10.1593/neo.08406
Hollander MC, Balogh AR, Liwanag J, Han W, Linnoila RI, Anver MR et al. Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice. Neoplasia. 2008 Aug;10(8):866-872. https://doi.org/10.1593/neo.08406
Hollander, Mary Christine ; Balogh, Andria R. ; Liwanag, Jaminelli ; Han, Wei ; Linnoila, Ritva Ilona ; Anver, Miriam R. ; Dennis, Phillip A. / Strain-specific spontaneous and NNK-mediated tumorigenesis in Pten+/- mice. In: Neoplasia. 2008 ; Vol. 10, No. 8. pp. 866-872.
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