Item Details

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

Sivec, Alexandra (author)

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

title

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

type

Thesis