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DIET MODULATED BILE ACID METABOLITES AND SIGNALING IN THE BREAST: IMPLICATIONS FOR BREAST CANCER

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title
DIET MODULATED BILE ACID METABOLITES AND SIGNALING IN THE BREAST: IMPLICATIONS FOR BREAST CANCER
author
Sivec, Alexandra
abstract
Triple negative breast cancer (TNBC) comprises approximately 15% of all breast cancer cases. Obesity is associated with an increased risk of TNBC in premenopausal women. Western diet consumption can impact the bile acid synthesis. In this study, we investigated whether diet differentially modulates bile acid metabolism within breast tissue that could impact TNBC risk. Global untargeted metabolomics of mammary tissue identified bile acid metabolites and semi-quantitative bile acid analysis in enteric tissue differentiated systematic or localized regulation of bile acid synthesis by diet. We observed a decrease in β-muricholate in all experimental diets and an increase in mammary tauro-deoxycholate of lard+safflower oil diet-fed mice not seen in enteric tissues. Elevated conjugated-to-unconjugated ratios of deoxycholate of high sugar diet-fed mice occurred in enteric tissues, but not mammary glands. We compared mammary and liver tissues expression of farnesoid X receptor (FXR), and observed a 10-fold increase in mammary FXR expression of lard diet-fed mice. A real-time cell analyzer evaluated the effects of bile acids directly on MDA-MB-231 and 4T1 TNBC cell index. Lithocholic acid decreased TNBC viability, while deoxycholic acid stimulated murine TNBC cell index. These findings suggest diet differentially modulates bile acid signaling within breast tissue and impact TNBC viability.
subject
Bile Acids
Diet
Farnesoid X Receptor
Mammary gland
Triple Negative Breast Cancer
contributor
Cook, Katherine L. (committee chair)
Kerr, Bethany A (committee member)
date
2021-01-13T09:35:28Z (accessioned)
2022-01-12T09:30:12Z (available)
2021 (issued)
degree
Biomedical Science – MS (discipline)
embargo
2022-01-12 (terms)
identifier
http://hdl.handle.net/10339/97958 (uri)
language
en (iso)
publisher
Wake Forest University
type
Thesis

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