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

Lipid exposure activates gene expression changes associated with estrogen receptor negative breast cancer.
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脂质暴露激活与雌激素受体阴性乳腺癌相关的基因表达变化。

DOI:
10.1038/s41523-022-00422-0
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发表时间:
2022-05-04
期刊:
影响因子:
5.9
通讯作者:
Clare SE
Clare SE
中科院分区:
医学2区
文献类型:
--
作者:
Yadav S;Virk R;Chung CH;Eduardo MB;VanDerway D;Chen D;Burdett K;Gao H;Zeng Z;Ranjan M;Cottone G;Xuei X;Chandrasekaran S;Backman V;Chatterton R;Khan SA;Clare SE

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提高对有助于雌激素受体阴性(ER−)乳腺癌(BC)发展的局部乳腺生物学的了解将促进更好的预防策略。我们先前已经证明,特定脂代谢基因的过度表达与ER−BC的发生有关。我们现在报告MCF-10A和MCF-12A细胞以及乳腺有机体对具有代表性的中链和长链多不饱和脂肪酸的暴露结果。这种暴露引起了基因表达的动态和深刻的变化,伴随着染色质堆积密度、染色质可及性和组蛋白翻译后修饰(PTM)的变化。我们确定了38个活性显著增加的代谢反应,包括与单碳代谢有关的反应。在这些反应中,有一些可以产生用于组蛋白PTMS的S-腺苷-L-蛋氨酸。利用体外模型和ER−BC高危女性的样本,我们发现脂质暴露产生了与ER−BC的发展相关的基因表达、信号通路激活和组蛋白标记。
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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