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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

DNA methyltransferase gene expression in mammary gland and tumor.Determination of DNMT1, DNMT3a and DNMT3b mRNA relative levels in mammary gland (a, b and c) and tumors (d, e and f) from all experimental groups at 246 days of age. Comparison of DNMT1(g), DNMT3a(h) and DNMT3b(i) mRNA relative levels between both tissues in each experimental group at 246 days of age. 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.g004: DNA methyltransferase gene expression in mammary gland and tumor.Determination of DNMT1, DNMT3a and DNMT3b mRNA relative levels in mammary gland (a, b and c) and tumors (d, e and f) from all experimental groups at 246 days of age. Comparison of DNMT1(g), DNMT3a(h) and DNMT3b(i) mRNA relative levels between both tissues in each experimental group at 246 days of age. 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: The mRNA relative levels of the maintenance DNA methyltransferase (DNMT1) and the de novo methyltransferases (DNMT3a and DNMT3b) were analyzed by real time PCR in mammary gland and in tumors at the end of the assay. The DNMT1 mRNA relative levels were always higher compared to DNMT3a and DNMT3b mRNA levels in both tissues and in all experimental groups (Fig 4). Expression levels of DNMT in mammary gland at 246 days of age showed a significant increase in DNMT1 mRNA levels in HCO (Fig 4a) and a decrease in DNMT3b mRNA in HOO compared to LF and HCO groups (Fig 4c). In tumors, we did not find significant differences in DNMT1 and DNMT3a mRNA relative levels among groups, although a trend to lower DNMT3a levels in EVOO groups was observed (Fig 4d and 4e). DNMT3b expression was decreased in HCO and in both high olive oil groups in comparison to the control (Fig 4f). We also compared values from mammary gland and tumor in each experimental group finding, in general, a decrease of DNMT expression in tumor, mainly in DNMT3a and DNMT3b (Fig 4 g–4i).


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)

DNA methyltransferase gene expression in mammary gland and tumor.Determination of DNMT1, DNMT3a and DNMT3b mRNA relative levels in mammary gland (a, b and c) and tumors (d, e and f) from all experimental groups at 246 days of age. Comparison of DNMT1(g), DNMT3a(h) and DNMT3b(i) mRNA relative levels between both tissues in each experimental group at 246 days of age. 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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Show All Figures
getmorefigures.php?uid=PMC4581736&req=5

pone.0138980.g004: DNA methyltransferase gene expression in mammary gland and tumor.Determination of DNMT1, DNMT3a and DNMT3b mRNA relative levels in mammary gland (a, b and c) and tumors (d, e and f) from all experimental groups at 246 days of age. Comparison of DNMT1(g), DNMT3a(h) and DNMT3b(i) mRNA relative levels between both tissues in each experimental group at 246 days of age. 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: The mRNA relative levels of the maintenance DNA methyltransferase (DNMT1) and the de novo methyltransferases (DNMT3a and DNMT3b) were analyzed by real time PCR in mammary gland and in tumors at the end of the assay. The DNMT1 mRNA relative levels were always higher compared to DNMT3a and DNMT3b mRNA levels in both tissues and in all experimental groups (Fig 4). Expression levels of DNMT in mammary gland at 246 days of age showed a significant increase in DNMT1 mRNA levels in HCO (Fig 4a) and a decrease in DNMT3b mRNA in HOO compared to LF and HCO groups (Fig 4c). In tumors, we did not find significant differences in DNMT1 and DNMT3a mRNA relative levels among groups, although a trend to lower DNMT3a levels in EVOO groups was observed (Fig 4d and 4e). DNMT3b expression was decreased in HCO and in both high olive oil groups in comparison to the control (Fig 4f). We also compared values from mammary gland and tumor in each experimental group finding, in general, a decrease of DNMT expression in tumor, mainly in DNMT3a and DNMT3b (Fig 4 g–4i).

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