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The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

Rodríguez-Miguel C, Moral R, Escrich R, Vela E, Solanas M, Escrich E - PLoS ONE (2015)

Bottom Line: Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging.The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3.These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Grup Multidisciplinari per a l'Estudi del Càncer de Mama, Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.

ABSTRACT
Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO) diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3) DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac) by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

No MeSH data available.


Related in: MedlinePlus

Global levels of histone 3 (H3K4me2, H3K27me3) and histone 4 (H4K20me3, H4K16ac) modifications in mammary gland and tumor.Representative images obtained for western blot data from mammary gland and tumor of histone 3 and histone 4 modifications (a). Determination of relative levels of such modifications in mammary gland (b) and tumor (c) from all experimental groups at 246 days of age. Comparison of global levels of histone modifications between both tissues (d) in each experimental group. Data shown represent medians of the groups. Full lines connecting groups indicate differences statistically significant (p<0.05); dotted lines indicate differences close to significance (p<0.1).
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pone.0138980.g006: Global levels of histone 3 (H3K4me2, H3K27me3) and histone 4 (H4K20me3, H4K16ac) modifications in mammary gland and tumor.Representative images obtained for western blot data from mammary gland and tumor of histone 3 and histone 4 modifications (a). Determination of relative levels of such modifications in mammary gland (b) and tumor (c) from all experimental groups at 246 days of age. Comparison of global levels of histone modifications between both tissues (d) in each experimental group. Data shown represent medians of the groups. Full lines connecting groups indicate differences statistically significant (p<0.05); dotted lines indicate differences close to significance (p<0.1).

Mentions: Global levels of histone 3 (H3K4me2, H3K27me3) and histone 4 (H4K20me3, H4K16ac) modifications have been determined in mammary gland and tumor at 246 days of age by western blotting (Fig 6a). In mammary gland, we found no clear differences of such histone modifications among experimental groups, except a significant decrease of H3K27me3 relative levels in HCO group compared to LF group, and a trend to decrease the H4K16ac relative levels in HOO group (Fig 6b). In tumors, the high fat diets did not significantly influence the relative levels of histone 3 modifications (H3K4me2, H3K27me3). Results of histone 4 modifications showed a decrease of H4K20me3 relative levels in LF-HOO group compared with all other groups, and a decrease of H4K16ac in LF-HOO compared to HOO group (Fig 6c). We also compared the global levels of histone 3 and histone 4 modifications between mammary gland and tumor in each experimental group at 246 days of age finding, in general, a decrease of such modifications in tumor (Fig 6d).


The Role of Dietary Extra Virgin Olive Oil and Corn Oil on the Alteration of Epigenetic Patterns in the Rat DMBA-Induced Breast Cancer Model.

Rodríguez-Miguel C, Moral R, Escrich R, Vela E, Solanas M, Escrich E - PLoS ONE (2015)

Global levels of histone 3 (H3K4me2, H3K27me3) and histone 4 (H4K20me3, H4K16ac) modifications in mammary gland and tumor.Representative images obtained for western blot data from mammary gland and tumor of histone 3 and histone 4 modifications (a). Determination of relative levels of such modifications in mammary gland (b) and tumor (c) from all experimental groups at 246 days of age. Comparison of global levels of histone modifications between both tissues (d) in each experimental group. Data shown represent medians of the groups. Full lines connecting groups indicate differences statistically significant (p<0.05); dotted lines indicate differences close to significance (p<0.1).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4581736&req=5

pone.0138980.g006: Global levels of histone 3 (H3K4me2, H3K27me3) and histone 4 (H4K20me3, H4K16ac) modifications in mammary gland and tumor.Representative images obtained for western blot data from mammary gland and tumor of histone 3 and histone 4 modifications (a). Determination of relative levels of such modifications in mammary gland (b) and tumor (c) from all experimental groups at 246 days of age. Comparison of global levels of histone modifications between both tissues (d) in each experimental group. Data shown represent medians of the groups. Full lines connecting groups indicate differences statistically significant (p<0.05); dotted lines indicate differences close to significance (p<0.1).
Mentions: Global levels of histone 3 (H3K4me2, H3K27me3) and histone 4 (H4K20me3, H4K16ac) modifications have been determined in mammary gland and tumor at 246 days of age by western blotting (Fig 6a). In mammary gland, we found no clear differences of such histone modifications among experimental groups, except a significant decrease of H3K27me3 relative levels in HCO group compared to LF group, and a trend to decrease the H4K16ac relative levels in HOO group (Fig 6b). In tumors, the high fat diets did not significantly influence the relative levels of histone 3 modifications (H3K4me2, H3K27me3). Results of histone 4 modifications showed a decrease of H4K20me3 relative levels in LF-HOO group compared with all other groups, and a decrease of H4K16ac in LF-HOO compared to HOO group (Fig 6c). We also compared the global levels of histone 3 and histone 4 modifications between mammary gland and tumor in each experimental group at 246 days of age finding, in general, a decrease of such modifications in tumor (Fig 6d).

Bottom Line: Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging.The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3.These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

View Article: PubMed Central - PubMed

Affiliation: Grup Multidisciplinari per a l'Estudi del Càncer de Mama, Physiology Unit, Department of Cell Biology, Physiology and Immunology, Faculty of Medicine, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.

ABSTRACT
Disruption of epigenetic patterns is a major change occurring in all types of cancers. Such alterations are characterized by global DNA hypomethylation, gene-promoter hypermethylation and aberrant histone modifications, and may be modified by environment. Nutritional factors, and especially dietary lipids, have a role in the etiology of breast cancer. Thus, we aimed to analyze the influence of different high fat diets on DNA methylation and histone modifications in the rat dimethylbenz(a)anthracene (DMBA)-induced breast cancer model. Female Sprague-Dawley rats were fed a low-fat, a high corn-oil or a high extra-virgin olive oil (EVOO) diet from weaning or from induction with DMBA. In mammary glands and tumors we analyzed global and gene specific (RASSF1A, TIMP3) DNA methylation by LUMA and bisulfite pyrosequencing assays, respectively. We also determined gene expression and enzymatic activity of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) and evaluated changes in histone modifications (H3K4me2, H3K27me3, H4K20me3 and H4K16ac) by western-blot. Our results showed variations along time in the global DNA methylation of the mammary gland displaying decreases at puberty and with aging. The olive oil-enriched diet, on the one hand, increased the levels of global DNA methylation in mammary gland and tumor, and on the other, changed histone modifications patterns. The corn oil-enriched diet increased DNA methyltransferase activity in both tissues, resulting in an increase in the promoter methylation of the tumor suppressor genes RASSF1A and TIMP3. These results suggest a differential effect of the high fat diets on epigenetic patterns with a relevant role in the neoplastic transformation, which could be one of the mechanisms of their differential promoter effect, clearly stimulating for the high corn-oil diet and with a weaker influence for the high EVOO diet, on breast cancer progression.

No MeSH data available.


Related in: MedlinePlus