Limits...
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 promoter methylation of RASSF1A and TIMP3 genes in mammary gland and tumor.Representative pyrogram of RASSF1A(a) and TIMP3(b) promoter methylation analyses. Determination of RASSF1A and TIMP3 DNA methylation in mammary gland (c, d) and tumor (e, f) from all experimental groups at 246 days of age. Comparison of RASSF1A(g) and TIMP3(h) gene methylation 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
getmorefigures.php?uid=PMC4581736&req=5

pone.0138980.g003: DNA promoter methylation of RASSF1A and TIMP3 genes in mammary gland and tumor.Representative pyrogram of RASSF1A(a) and TIMP3(b) promoter methylation analyses. Determination of RASSF1A and TIMP3 DNA methylation in mammary gland (c, d) and tumor (e, f) from all experimental groups at 246 days of age. Comparison of RASSF1A(g) and TIMP3(h) gene methylation 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 promoter methylation of RASSF1A (Fig 3a) and TIMP3 (Fig 3b) genes were determined in bisulfite-modified DNAs from mammary glands and tumors at 246 days. In mammary gland, both groups fed the corn oil-enriched diet had significant increased values of RASSF1A methylation compared to LF group. Values from HCO were also significantly higher than those from HOO (Fig 3c). TIMP3 mehtylation was also increased in HCO group compared to LF and high extra virgin olive oil groups (Fig 3d). In tumors, the methylation levels of RASSF1A increased in all high fat diet groups except in LF-HCO (Fig 3e). TIMP3 promoter methylation tended to increase in HCO group versus the control, whilst the LF-HOO group had significantly lower levels compared with all other high fat groups (Fig 3f). Finally, comparison between tissues showed an increase in both RASSF1A and TIMP3 promoter methylation in tumors, compared to mammary glands, in all the experimental groups. (Fig 3g and 3h).


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 promoter methylation of RASSF1A and TIMP3 genes in mammary gland and tumor.Representative pyrogram of RASSF1A(a) and TIMP3(b) promoter methylation analyses. Determination of RASSF1A and TIMP3 DNA methylation in mammary gland (c, d) and tumor (e, f) from all experimental groups at 246 days of age. Comparison of RASSF1A(g) and TIMP3(h) gene methylation 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.g003: DNA promoter methylation of RASSF1A and TIMP3 genes in mammary gland and tumor.Representative pyrogram of RASSF1A(a) and TIMP3(b) promoter methylation analyses. Determination of RASSF1A and TIMP3 DNA methylation in mammary gland (c, d) and tumor (e, f) from all experimental groups at 246 days of age. Comparison of RASSF1A(g) and TIMP3(h) gene methylation 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 promoter methylation of RASSF1A (Fig 3a) and TIMP3 (Fig 3b) genes were determined in bisulfite-modified DNAs from mammary glands and tumors at 246 days. In mammary gland, both groups fed the corn oil-enriched diet had significant increased values of RASSF1A methylation compared to LF group. Values from HCO were also significantly higher than those from HOO (Fig 3c). TIMP3 mehtylation was also increased in HCO group compared to LF and high extra virgin olive oil groups (Fig 3d). In tumors, the methylation levels of RASSF1A increased in all high fat diet groups except in LF-HCO (Fig 3e). TIMP3 promoter methylation tended to increase in HCO group versus the control, whilst the LF-HOO group had significantly lower levels compared with all other high fat groups (Fig 3f). Finally, comparison between tissues showed an increase in both RASSF1A and TIMP3 promoter methylation in tumors, compared to mammary glands, in all the experimental groups. (Fig 3g and 3h).

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