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

doi:10.1038/s41523-022-00422-0

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

NPJ Breast Cancer. 2022 May 4;8(1):59. doi: 10.1038/s41523-022-00422-0.

Authors

Shivangi Yadav¹, Ranya Virk², Carolina H Chung³, Mariana Bustamante Eduardo¹, David VanDerway², Duojiao Chen⁴, Kirsten Burdett⁵, Hongyu Gao⁴, Zexian Zeng⁶, Manish Ranjan¹, Gannon Cottone¹, Xiaoling Xuei⁴, Sriram Chandrasekaran^{3

7

8

9}, Vadim Backman², Robert Chatterton¹⁰, Seema Ahsan Khan¹¹, Susan E Clare¹²

Affiliations

¹ Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
² Department of Biomedical Engineering, Northwestern University, Evanston, IL, 60208-2850, USA.
³ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
⁴ Center of for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
⁵ Department of Preventive Medicine, Northwestern University, Chicago, IL, 60611, USA.
⁶ Department of Data Sciences, Dana Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, 02215, USA.
⁷ Program in Chemical Biology, University of Michigan, Ann Arbor, MI, 48109, USA.
⁸ Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
⁹ Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁰ Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
¹¹ Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. s-khan2@northwestern.edu.
¹² Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. susan.clare@northwestern.edu.

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.

Abstract

Grants and funding