BACKGROUND: The effects of dietary polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on intestinal cytokinetics within the context of colon cancer initiation and progression have been extensively studied. n-3 PUFAs have received the most attention due to their potential protective role. However, further investigation of the epigenetic perturbations caused by fatty acids in the context of colon cancer development is needed. METHODS: We used DNA microarrays to identify discriminative gene signatures (gene combinations) for the purpose of classifying n-3 PUFA-fed, carcinogen-injected, Sprague-Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differing only in the type of fat (corn oil/n-6 PUFA, fish oil/n-3 PUFA, or olive oil/n-9 monounsaturated fatty acid). RESULTS: The effects of diet on colonic mucosal gene expression signatures during tumor initiation and progression were subsequently compared (12 h and 10 weeks after azoxymethane injection). Microarray analysis revealed that the number of differentially expressed (DE) genes in each of the three diet comparisons increased with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach, we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective (fish oil) diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-performing gene classifiers. CONCLUSIONS: These results suggest that dietary chemoprotective n-3 PUFA impact genes that regulate the colon stem cell niche and tumor evolution.
BACKGROUND: The effects of dietary polyunsaturated (PUFAs) and monounsaturated fatty acids (MUFAs) on intestinal cytokinetics within the context of colon cancer initiation and progression have been extensively studied. n-3 PUFAs have received the most attention due to their potential protective role. However, further investigation of the epigenetic perturbations caused by fatty acids in the context of colon cancer development is needed. METHODS: We used DNA microarrays to identify discriminative gene signatures (gene combinations) for the purpose of classifying n-3 PUFA-fed, carcinogen-injected, Sprague-Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differing only in the type of fat (cornoil/n-6 PUFA, fish oil/n-3 PUFA, or oliveoil/n-9 monounsaturated fatty acid). RESULTS: The effects of diet on colonic mucosal gene expression signatures during tumor initiation and progression were subsequently compared (12 h and 10 weeks after azoxymethane injection). Microarray analysis revealed that the number of differentially expressed (DE) genes in each of the three diet comparisons increased with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach, we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective (fish oil) diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-performing gene classifiers. CONCLUSIONS: These results suggest that dietary chemoprotective n-3 PUFA impact genes that regulate the colon stem cell niche and tumor evolution.
Authors: Mee Young Hong; Robert S Chapkin; Rola Barhoumi; Robert C Burghardt; Nancy D Turner; Cara E Henderson; Lisa M Sanders; Yang-Yi Fan; Laurie A Davidson; Mary E Murphy; Christine M Spinka; Raymond J Carroll; Joanne R Lupton Journal: Carcinogenesis Date: 2002-11 Impact factor: 4.944
Authors: Laurie A Davidson; Danh V Nguyen; Regina M Hokanson; Evelyn S Callaway; Robert B Isett; Nancy D Turner; Edward R Dougherty; Naisyin Wang; Joanne R Lupton; Raymond J Carroll; Robert S Chapkin Journal: Cancer Res Date: 2004-09-15 Impact factor: 12.701
Authors: Qian Jia; Joanne R Lupton; Roger Smith; Brad R Weeks; Evelyn Callaway; Laurie A Davidson; Wooki Kim; Yang-Yi Fan; Peiying Yang; Robert A Newman; Jing X Kang; David N McMurray; Robert S Chapkin Journal: Cancer Res Date: 2008-05-15 Impact factor: 12.701
Authors: A Bedi; P J Pasricha; A J Akhtar; J P Barber; G C Bedi; F M Giardiello; B A Zehnbauer; S R Hamilton; R J Jones Journal: Cancer Res Date: 1995-05-01 Impact factor: 12.701
Authors: Youngmi Cho; Hyemee Kim; Nancy D Turner; John C Mann; Jiawei Wei; Stella S Taddeo; Laurie A Davidson; Naisyin Wang; Marina Vannucci; Raymond J Carroll; Robert S Chapkin; Joanne R Lupton Journal: J Nutr Date: 2011-04-20 Impact factor: 4.798
Authors: Laurie A Davidson; Jennifer S Goldsby; Evelyn S Callaway; Manasvi S Shah; Nick Barker; Robert S Chapkin Journal: Biochim Biophys Acta Date: 2012-06-30
Authors: Jan S Suchodolski; Melissa E Markel; Jose F Garcia-Mazcorro; Stefan Unterer; Romy M Heilmann; Scot E Dowd; Priyanka Kachroo; Ivan Ivanov; Yasushi Minamoto; Enricka M Dillman; Jörg M Steiner; Audrey K Cook; Linda Toresson Journal: PLoS One Date: 2012-12-26 Impact factor: 3.240