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

4 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

Funding

We would like to thank Professors Matthew D Hirschey and Neil Kelleher for advice regarding histone proteomics and, Jeannie Camarillo and the Northwestern Proteomics Core for conducting the histone proteomic analysis; The Northwest Metabolic Research Center (NW-MRC) at University of Washington for performing the lipidomics analysis; The Center for Medical Genomics at the Indiana University School of Medicine for RNA library preparation and RNA sequencing, and ATAC sequencing; The NU Seq Core facility for providing The QuantStudio 7 Flex system; Natalie Pulliam for consenting patients and collecting tissue, and our many lab colleagues for feedback. This work was supported by the Breast Cancer Research Foundation (S.A.K.), Bramsen-Hamill Foundation (S.A.K.), Otzen Family Foundation (S.E.C.), Ulla and Bertil Brunk Foundation (S.E.C.), R35 GM13779501 from The National Institute of General Medical Sciences, NIH (S.C.). We would like to thank Professors Matthew D Hirschey and Neil Kelleher for advice regarding histone proteomics and, Jeannie Camarillo and the Northwestern Proteomics Core for conducting the histone proteomic analysis; The Northwest Metabolic Research Center (NW-MRC) at University of Washington for performing the lipidomics analysis; The Center for Medical Genomics at the Indiana University School of Medicine for RNA library preparation and RNA sequencing, and ATAC sequencing; The NU Seq Core facility for providing The QuantStudio 7 Flex system; Natalie Pulliam for consenting patients and collecting tissue, and our many lab colleagues for feedback. This work was supported by the Breast Cancer Research Foundation (S.A.K.), Bramsen-Hamill Foundation (S.A.K.), Otzen Family Foundation (S.E.C.), Ulla and Bertil Brunk Foundation (S.E.C.), R35 GM13779501 from The National Institute of General Medical Sciences, NIH (S.C.).

ASJC Scopus subject areas

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

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