Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer

Shivangi Yadav, Ranya Virk, Carolina H. Chung, Mariana Bustamante Eduardo, David VanDerway, Duojiao Chen, Kirsten Burdett, Hongyu Gao, Zexian Zeng, Manish Ranjan, Gannon Cottone, Xiaoling Xuei, Sriram Chandrasekaran, Vadim Backman, Robert Chatterton, Seema Ahsan Khan*, Susan E. Clare

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Improved understanding of local breast biology that favors the development of estrogen receptor negative (ER−) breast cancer (BC) would foster better prevention strategies. We have previously shown that overexpression of specific lipid metabolism genes is associated with the development of ER− BC. We now report results of exposure of MCF-10A and MCF-12A cells, and mammary organoids to representative medium- and long-chain polyunsaturated fatty acids. This exposure caused a dynamic and profound change in gene expression, accompanied by changes in chromatin packing density, chromatin accessibility, and histone posttranslational modifications (PTMs). We identified 38 metabolic reactions that showed significantly increased activity, including reactions related to one-carbon metabolism. Among these reactions are those that produce S-adenosyl-L-methionine for histone PTMs. Utilizing both an in-vitro model and samples from women at high risk for ER− BC, we show that lipid exposure engenders gene expression, signaling pathway activation, and histone marks associated with the development of ER− BC.

Original languageEnglish (US)
Article number59
Journalnpj Breast Cancer
Volume8
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer'. Together they form a unique fingerprint.

Cite this