TY - JOUR
T1 - Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer
AU - Yadav, Shivangi
AU - Virk, Ranya
AU - Chung, Carolina H.
AU - Eduardo, Mariana Bustamante
AU - VanDerway, David
AU - Chen, Duojiao
AU - Burdett, Kirsten
AU - Gao, Hongyu
AU - Zeng, Zexian
AU - Ranjan, Manish
AU - Cottone, Gannon
AU - Xuei, Xiaoling
AU - Chandrasekaran, Sriram
AU - Backman, Vadim
AU - Chatterton, Robert
AU - Khan, Seema Ahsan
AU - Clare, Susan E.
N1 - Funding Information:
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.).
Funding Information:
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.).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85129634483&partnerID=8YFLogxK
U2 - 10.1038/s41523-022-00422-0
DO - 10.1038/s41523-022-00422-0
M3 - Article
C2 - 35508495
AN - SCOPUS:85129634483
SN - 2374-4677
VL - 8
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 59
ER -
