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Influence of Fatty Acid Diets on Gene Expression in Rat Mammary Epithelial Cells


ABSTRACT: Background: This study examines the impact of dietary fatty acids on regulation of gene expression in the mammary epithelial cells before and during puberty. Methods: The diets primarily consisted of n-9 monounsaturated fatty acids (olive oil), n-6 polyunsaturated fatty acids (safflower), saturated acids (butter), and the reference AIN-93G diet (soy oil). The dietary regimen mimics the repetitive nature of fatty acid exposure in Western diets. Dietary-induced changes in gene expression were examined in the LCM (Laser Capture Microdissected) captured mammary ductal epithelial cells at day of weaning (21 days) and at the end of puberty (50 days after birth). PCNA immunohistochemistry analysis was used to compare proliferation rates between diets. Results: Genes differentially expressed between each of the test diets and the reference diet in both age groups were significantly enriched by cell cycle genes. Some of these genes were involved in the activation of the cell cycle pathway or the G2/M check point pathway. Although there were some differences in the level of differential expression, all diets showed qualitatively same pattern of differential expression compared to the reference diet. Cluster analysis identified an expanded set of cell cycle as well as immunity and sterol metabolism related clusters of differentially expressed genes. Conclusion: Fatty acid-enriched diets significantly up-regulated proliferation above the normal physiological level at day 50. The higher cellular proliferation during puberty caused by enriched fatty acid diets pose a potential increase risk of mammary cancer in later life. The human homologs of 27 of 62 cell cycle cluster of rat genes are included in a human breast cancer cluster of 45 cell cycle related genes further emphasizing the importance of our findings in the rat model. Female, virgin Spraque-Dawley rats were obtained from Taconic Farms (Germantown, NY) at approximately 7 weeks of age and placed on one of 9 pelleted purified diets for one month. After one month of diet exposure, female rats were bred with male Sprague-Dawley rats of approximately 3 months of age. Litters were weighed and monitored throughout gestational period. Pups had access to dam’s milk as well as tap water and food throughout gestation. Pups were weaned at DOL 21 and individually housed with tap water and diets ad libitum. Rats were killed by CO2 asphyxiation and decapitated at the following two ages, DOW (DOL21) and DOL 50 with no other treatments.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Johannes Freudenberg 

PROVIDER: E-GEOD-14933 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Influence of fatty acid diets on gene expression in rat mammary epithelial cells.

Medvedovic M M   Gear R R   Freudenberg J M JM   Schneider J J   Bornschein R R   Yan M M   Mistry M J MJ   Hendrix H H   Karyala S S   Halbleib D D   Heffelfinger S S   Clegg D J DJ   Anderson M W MW  

Physiological genomics 20090407 1


<h4>Background</h4>This study examines the impact of dietary fatty acids on regulation of gene expression in mammary epithelial cells before and during puberty.<h4>Methods</h4>Diets primarily consisted of n-9 monounsaturated fatty acids (olive oil), n-6 polyunsaturated fatty acids (safflower), saturated acids (butter), and the reference AIN-93G diet (soy oil). The dietary regimen mimics the repetitive nature of fatty acid exposure in Western diets. Diet-induced changes in gene expression were ex  ...[more]

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