The impacts of chronic bisphenol A (BPA) exposure suspected to be a potential risk factor for breast cancer progression are not thoroughly understood in different subtypes of breast cancer cells (BCCs). This study aimed to compare the differentially expressed genes (DEGs) and biological functions in MCF-7 (luminal A), SK-BR3 (HER2-enriched) and MDA-MB-231 (triple-negative) cells exposed to BPA at an environmentally human-relevant low dose (10-8 M) for 30 days, by using the approach of RNA sequencing and online informatics tools. BPA-exposure resulted in 172, 137, and 139 DEGs in MCF-7/BPA, SK-BR3/BPA, and MDA-MB-231/BPA, respectively. The significantly enriched gene ontology terms of DEGs in each cell were different: cellular response to gonadotropin-releasing hormone, negative regulation of fibrinolysis, choline metabolism, glutamate signaling pathways and coagulation pathway in MCF-7/BPA; positive regulation of inflammatory response and VEGF/VEGFR signaling pathways in SK-BR3/BPA; negative regulation of keratinocyte proliferation and HIF signaling pathways in MDA-MB-231/BPA cells. The immune network analysis of DEGs across the breast cancer cells indicated NKT, NK and T cell activation and dendritic cell migration by regulating the expression of immunomodulatory genes. High expression of IL19, CA9 and SPARC identified in MCF-7/BPA, SK-BR3/BPA, and MDA-MB-231/BPA are detrimental gene signatures to predict poor overall survival in luminal A, HER2-enriched and triple-negative breast cancer patients, respectively. These findings indicate chronic BPA exposure has dissimilar impacts on the regulation of gene expression and diverse biological functions, including immune modulation, in different subtypes of BCCs.

中文翻译：

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长期暴露于不同亚型乳腺癌细胞中的低剂量双酚A导致的转录组表达变化的比较。

在不同亚型的乳腺癌细胞（BCC）中，尚未完全了解怀疑长期双酚A（BPA）暴露可能是导致乳腺癌发展的潜在危险因素的影响。这项研究旨在比较在环境中暴露于BPA的MCF-7（腔A），SK-BR3（富含HER2）和MDA-MB-231（三阴性）细胞中的差异表达基因（DEG）和生物学功能。通过使用RNA测序和在线信息学工具，在30天内与人相关的低剂量（10-8 M）。BPA接触导致MCF-7 / BPA，SK-BR3 / BPA和MDA-MB-231 / BPA分别产生172、137和139个DEG。每个细胞中DEG的显着丰富的基因本体术语是不同的：细胞对促性腺激素释放激素的反应，纤维蛋白溶解的负调节，胆碱代谢，MCF-7 / BPA中的谷氨酸信号传导途径和凝血途径；在SK-BR3 / BPA中积极调节炎症反应和VEGF / VEGFR信号通路；MDA-MB-231 / BPA细胞中角质形成细胞增殖和HIF信号通路的负调控。跨乳腺癌细胞的DEG免疫网络分析表明，通过调节免疫调节基因的表达，NKT，NK和T细胞活化以及树突状细胞迁移。在MCF-7 / BPA，SK-BR3 / BPA和MDA-MB-231 / BPA中鉴定到的IL19，CA9和SPARC的高表达是有害的基因特征，无法预测管腔A，富含HER2的三阴性细胞的总生存期。乳腺癌患者。这些发现表明，长期接触BPA对基因表达的调节和多种生物学功能有不同的影响，