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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

RASSF1A and TIMP3 gene expression in mammary gland and tumor.Determination of RASSF1A(a) and TIMP3(b) mRNA relative levels in mammary gland from all experimental groups along time. Determination of RASSF1A(c) and TIMP3(d) mRNA relative levels in tumors from all experimental groups at 246 days of age. Comparison of RASSF1A(e) and TIMP3(f) 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.g002: RASSF1A and TIMP3 gene expression in mammary gland and tumor.Determination of RASSF1A(a) and TIMP3(b) mRNA relative levels in mammary gland from all experimental groups along time. Determination of RASSF1A(c) and TIMP3(d) mRNA relative levels in tumors from all experimental groups at 246 days of age. Comparison of RASSF1A(e) and TIMP3(f) 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: Results for RASSF1A and TIMP3 gene expression in mammary gland showed a great variability along time, displaying different trends in adolescence (36 and 51 days) and in adulthood (100 and 246 days of age). The RASSF1A gene expression showed a maximum at 100 days in all groups (except HCO) and a decrease thereafter (Fig 2a). The TIMP3 gene expression decreased along time in all high fat groups, while reached its maximum at 100 days of age in LF group (Fig 2b). The high fat diets did not modify RASSF1A expression at the ages tested. TIMP3 expression decreased in LF-HCO group compared to LF group at the end of the assay (246 days) (Fig 2b). In tumors, RASSF1A gene expression showed a significant decrease in both high olive oil groups in relation to LF and high corn oil groups (Fig 2c), while TIMP3 expression was lower in LF-HOO group compared with the LF control (Fig 2d). Comparison between tissues showed a significant decrease in the expression of both genes in tumors in all experimental groups (Fig 2e and 2f).


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)

RASSF1A and TIMP3 gene expression in mammary gland and tumor.Determination of RASSF1A(a) and TIMP3(b) mRNA relative levels in mammary gland from all experimental groups along time. Determination of RASSF1A(c) and TIMP3(d) mRNA relative levels in tumors from all experimental groups at 246 days of age. Comparison of RASSF1A(e) and TIMP3(f) 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

License
Show All Figures
getmorefigures.php?uid=PMC4581736&req=5

pone.0138980.g002: RASSF1A and TIMP3 gene expression in mammary gland and tumor.Determination of RASSF1A(a) and TIMP3(b) mRNA relative levels in mammary gland from all experimental groups along time. Determination of RASSF1A(c) and TIMP3(d) mRNA relative levels in tumors from all experimental groups at 246 days of age. Comparison of RASSF1A(e) and TIMP3(f) 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: Results for RASSF1A and TIMP3 gene expression in mammary gland showed a great variability along time, displaying different trends in adolescence (36 and 51 days) and in adulthood (100 and 246 days of age). The RASSF1A gene expression showed a maximum at 100 days in all groups (except HCO) and a decrease thereafter (Fig 2a). The TIMP3 gene expression decreased along time in all high fat groups, while reached its maximum at 100 days of age in LF group (Fig 2b). The high fat diets did not modify RASSF1A expression at the ages tested. TIMP3 expression decreased in LF-HCO group compared to LF group at the end of the assay (246 days) (Fig 2b). In tumors, RASSF1A gene expression showed a significant decrease in both high olive oil groups in relation to LF and high corn oil groups (Fig 2c), while TIMP3 expression was lower in LF-HOO group compared with the LF control (Fig 2d). Comparison between tissues showed a significant decrease in the expression of both genes in tumors in all experimental groups (Fig 2e and 2f).

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