Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice.
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)-Kras(G12D) (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.
Cheon
Eric C
EC
Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Strouch
Matthew J
MJ
Barron
Morgan R
MR
Ding
Yongzeng
Y
Melstrom
Laleh G
LG
Krantz
Seth B
SB
Mullapudi
Bhargava
B
Adrian
Kevin
K
Rao
Sambasiva
S
Adrian
Thomas E
TE
Bentrem
David J
DJ
Grippo
Paul J
PJ
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D049109:Cell Proliferation; D017931:DNA Primers; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage*; D011905:Genes, ras; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D013045:Species Specificity
D017931:DNA Primers; D043371:Fatty Acids, Omega-6