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

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

doi:10.1002/ijc.25622

Cited by 25 publications

(26 citation statements)

References 32 publications

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“…In flaxseed and in fish oil, n-3 polyunsaturated FAs (n3PUFAs) also contribute as principal FAs [1]. Previous studies have shown that increased FAs regulate pancreatic cancer [2][3][4][5][6][7][8]. For instance, diets rich in SFAs and n6PUFAs accelerate the process of pancreatic carcinogenesis in the animal, whereas HFDs made of fish oil and thus rich in n3PUFAs sometimes inhibit the carcinogenetic process [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Four types of fatty acids exert differential impact on pancreatic cancer growth

Yu¹,

Liu²,

Duan³

et al. 2015

Cancer Letters

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Section: Introductionmentioning

confidence: 99%

Four types of fatty acids exert differential impact on pancreatic cancer growth

Yu¹,

Liu²,

Duan³

et al. 2015

Cancer Letters

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“…We have previously demonstrated that EL-Kras mice fed a diet rich in omega-6 fatty acids have increased lesion numbers and increased mast cell infiltration [16]. Since LTB4 is a potent chemotactic factor for mast cells [12], we extended these findings into human cells by determining the effect of omega-6 fatty acids on LTB4 production in vitro .…”

Section: Resultsmentioning

confidence: 99%

“…Previously, we reported that EL-Kras mice fed diets rich in omega-6 fatty acids demonstrated increased pancreatic mast cell infiltration [16]. Significantly, increased infiltration of mast cells into the tumor microenvironment correlates with a poor prognosis [15].…”

Section: Discussionmentioning

confidence: 99%

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Ablation of 5-lipoxygenase mitigates pancreatic lesion development

Knab

Schultz

Principe

et al. 2015

Journal of Surgical Research

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Background Pancreatic ductal adenocarcinoma (PDAC), which continues to have a dismal prognosis, is associated with a pronounced fibro-inflammatory response. Inflammation in vivo can be mediated by 5-lipoxygenase (5LO), an enzyme that converts omega-6 fatty acids to eicosanoids, including leukotriene B4 (LTB4). We have previously shown that diets rich in omega-6 fatty acids (FA) increase pancreatic lesions and mast cell infiltration in EL-Kras mice. In this study, we evaluated the role of 5LO in generating higher levels of LTB4 from human cells and in mediating lesion development and mast cell infiltration in EL-Kras mice. Materials and Methods Human pancreatic ductal epithelial (HPDE) and cancer cells were treated with omega-6 FA in vitro. EL-Kras mice lacking 5LO (EL-Kras/5LO−/−) mice were generated and fed standard chow or omega-6 FA diets. Pancreatic lesion frequency and mast cell infiltration were compared to EL-Kras/5LO+/+ mice. Human PDAC tumors were evaluated for 5LO expression and mast cells. Results HPDE and cancer cells treated with omega-6 FA generated increased LTB4 levels in vitro. EL-Kras/5LO−/− developed fewer pancreatic lesions and had decreased mast cell infiltration when compared to EL-Kras/5LO+/+ mice. Human PDAC tumors with increased 5LO expression demonstrate increased mast cell infiltration. Additionally, diets rich in omega-6 FA failed to increase pancreatic lesion development and mast cell infiltration in EL-Kras/5LO−/− mice. Conclusions The expansion of mutant Kras-induced lesions via omega-6 FA is dependent on 5LO, and 5LO functions downstream of mutant Kras to mediate inflammation, suggesting that 5LO may be a potential chemo-preventive and therapeutic target in pancreatic cancer.

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“…140 Obesity and a high fat diet are directly linked with the incidence of human pancreatic cancer. 141–143 …”

Section: Regulation Of Metabolic Activity By Mirnasmentioning

confidence: 99%

MicroRNAs in pancreatic cancer metabolism

Singh

Brand

Mehla

2012

Nat Rev Gastroenterol Hepatol

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Advances in understanding the biology of tumour progression and metastasis have clearly highlighted the importance of aberrant tumour metabolism, which supports not only the energy requirements but also the enormous biosynthetic needs of tumour cells. Such metabolic alterations modulate glucose, amino acid and fatty-acid-dependent metabolite bio-synthesis and energy production. Although much progress has been made in understanding the somatic mutations and expression genomics behind these alterations, the regulation of these processes by microRNAs (miRNAs) is only beginning to be appreciated. This Review focuses on the miRNAs that are potential regulators of the expression of genes whose protein products either directly regulate metabolic machinery or serve as master regulators, indirectly modulating the expression of metabolic enzymes. We focus particularly on miRNAs in pancreatic cancer.

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

Cited by 25 publications

References 32 publications

Four types of fatty acids exert differential impact on pancreatic cancer growth

Four types of fatty acids exert differential impact on pancreatic cancer growth

Ablation of 5-lipoxygenase mitigates pancreatic lesion development

MicroRNAs in pancreatic cancer metabolism

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