Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice

Eric C Cheon, Matthew J. Strouch, Morgan R. Barron, Yongzeng Ding, Laleh G. Melstrom, Seth B. Krantz, Bhargava Mullapudi, Kevin Adrian, Sambasiva Rao Musunuri, Thomas E. Adrian, David Jason Bentrem, Paul J. Grippo

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21 Scopus citations

Abstract

Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-KrasG12D (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid.

Original languageEnglish (US)
Pages (from-to)2783-2792
Number of pages10
JournalInternational Journal of Cancer
Volume128
Issue number12
DOIs
StatePublished - Jun 15 2011

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Keywords

  • Kras
  • omega-6
  • pancreatic cancer
  • strain

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cheon, E. C., Strouch, M. J., Barron, M. R., Ding, Y., Melstrom, L. G., Krantz, S. B., Mullapudi, B., Adrian, K., Musunuri, S. R., Adrian, T. E., Bentrem, D. J., & Grippo, P. J. (2011). Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice. International Journal of Cancer, 128(12), 2783-2792. https://doi.org/10.1002/ijc.25622