ArticleClinical cancer research : an official journal of the American Association for Cancer Research2009
Epidermal growth factor receptor is required for colonic tumor promotion by dietary fat in the azoxymethane/dextran sulfate sodium model: roles of transforming growth factor-{alpha} and PTGS2.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 38 citations in OpenAlex.
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- Losartan and Vitamin D Inhibit Colonic Tumor Development in a Conditional Apc-Deleted Mouse Model of Sporadic Colon Cancer.Cancer prevention research (Philadelphia, Pa.) · 2019Article
- Two sides to colon cancer: mice mimic human anatomical region disparity in colon cancer development and progression.Journal of cancer metastasis and treatment · 2018Article
- EGFR in Tumor-Associated Myeloid Cells Promotes Development of Colorectal Cancer in Mice and Associates With Outcomes of Patients.Gastroenterology · 2017Article
- ADAM17 is a Tumor Promoter and Therapeutic Target in Western Diet-associated Colon Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Linking Diet to Colorectal Cancer: The Emerging Role of MicroRNA in the Communication between Plant and Animal Kingdoms.Frontiers in microbiology · 2017Review
- Colon cancer and the epidermal growth factor receptor: Current treatment paradigms, the importance of diet, and the role of chemoprevention.World journal of clinical oncology · 2015Review
- The Role of Aspirin, Vitamin D, Exercise, Diet, Statins, and Metformin in the Prevention and Treatment of Colorectal Cancer.Current treatment options in oncology · 2015Review
- The renin-angiotensin system mediates EGF receptor-vitamin d receptor cross-talk in colitis-associated colon cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Divergent effects of muscarinic receptor subtype gene ablation on murine colon tumorigenesis reveals association of M3R and zinc finger protein 277 expression in colon neoplasia.Molecular cancer · 2014Article
- Both stromal cell and colonocyte epidermal growth factor receptors control HCT116 colon cancer cell growth in tumor xenografts.Carcinogenesis · 2012Article
- Epidermal growth factor receptor inhibits colitis-associated cancer in mice.The Journal of clinical investigation · 2012Article
- American ginseng suppresses Western diet-promoted tumorigenesis in model of inflammation-associated colon cancer: role of EGFR.BMC complementary and alternative medicine · 2011Article
- MicroRNA, nutrition, and cancer prevention.Advances in nutrition (Bethesda, Md.) · 2011Review
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
purposeColon cancer is a major cause of cancer deaths. Dietary factors contribute substantially to the risk of this malignancy. Western-style diets promote development of azoxymethane-induced colon cancer. Although we showed that epidermal growth factor receptors (EGFR) controlled azoxymethane tumorigenesis in standard fat conditions, the role of EGFR in tumor promotion by high dietary fat has not been examined. EXPERIMENTAL
designA/J x C57BL6/J mice with wild-type Egfr (Egfr(wt)) or loss-of-function waved-2 Egfr (Egfr(wa2)) received azoxymethane followed by standard (5% fat) or western-style (20% fat) diet. As F(1) mice were resistant to azoxymethane, we treated mice with azoxymethane followed by one cycle of inflammation-inducing dextran sulfate sodium to induce tumorigenesis. Mice were sacrificed 12 weeks after dextran sulfate sodium. Tumors were graded for histology and assessed for EGFR ligands and proto-oncogenes by immunostaining, Western blotting, and real-time PCR.
resultsEgfr(wt) mice gained significantly more weight and had exaggerated insulin resistance compared with Egfr(wa2) mice on high-fat diet. Dietary fat promoted tumor incidence (71.2% versus 36.7%; P < 0.05) and cancer incidence (43.9% versus 16.7%; P < 0.05) only in Egfr(wt) mice. The lipid-rich diet also significantly increased tumor and cancer multiplicity only in Egfr(wt) mice. In tumors, dietary fat and Egfr(wt) upregulated transforming growth factor-alpha, amphiregulin, CTNNB1, MYC, and CCND1, whereas PTGS2 was only increased in Egfr(wt) mice and further upregulated by dietary fat. Notably, dietary fat increased transforming growth factor-alpha in normal colon.
conclusionsEGFR is required for dietary fat-induced weight gain and tumor promotion. EGFR-dependent increases in receptor ligands and PTGS2 likely drive diet-related tumor promotion.
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