Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Int J Oncol. 2018 Aug;53(2):694-702. doi: 10.3892/ijo.2018.4436. Epub 2018 Jun 11.
The expression levels of estrogen receptor 1 (ESR1), arylamine N‑acetyltransferase 1 (NAT1), and arylamine N‑acetyltransferase 2 (NAT2) are implicated in breast cancer; however, their co-expression profiles in normal breast tissue, primary breast tumors and established breast cancer cell lines are undefined. NAT1 expression is widely reported to be associated with ESR1 expression and is frequently investigated in breast cancer etiology. Furthermore, the NAT2 phenotype has been reported to modify breast cancer risk in molecular epidemiological association studies. Understanding the relationships between the expression levels of these genes is essential to understand their role in breast cancer etiology and treatment. In the present study, NAT1, NAT2 and ESR1 expression data were accessed from repositories of RNA‑Seq data covering 57 breast cancer cell lines, 1,043 primary breast tumors and 99 normal breast tissues. The relationships between gene expression, and between NAT1 activity and RNA expression in breast cancer cell lines were evaluated using non-parametric statistical analyses. Differences in gene expression in each dataset, as well as gene expression differences in normal breast tissue compared to primary breast tumors, and stratification by estrogen receptor status were determined. NAT1 and NAT2 mRNA expression were detected in normal and primary breast tumor tissues; NAT1 expression was much higher than NAT2. NAT1 and ESR1 expression were strongly associated, whereas NAT2 and ESR1 expression were not. Although NAT1 and NAT2 expression were associated, the magnitude was moderate. NAT1, NAT2, and ESR1 expression were increased in primary breast tumor tissue compared with normal breast tissue; however, the magnitude and significance of the differences were lower for NAT2. Analysis of NAT1, NAT2, and ESR1 expression in normal and primary breast tissues and breast cancer cell lines suggested that NAT1 and NAT2 expression are regulated by distinctive mechanisms, whereas NAT1 and ESR1 expression may have overlapping regulation. Defining these relationships is important for future investigations into breast cancer prevention.
雌激素受体 1（ESR1）、芳香胺 N-乙酰转移酶 1（NAT1）和芳香胺 N-乙酰转移酶 2（NAT2）的表达水平与乳腺癌有关；然而，它们在正常乳腺组织、原发性乳腺癌肿瘤和已建立的乳腺癌细胞系中的共表达谱尚未确定。NAT1 表达广泛报道与 ESR1 表达相关，并且经常在乳腺癌病因学中进行研究。此外，NAT2 表型已被报道在分子流行病学关联研究中改变乳腺癌风险。了解这些基因表达水平之间的关系对于理解它们在乳腺癌病因学和治疗中的作用至关重要。在本研究中，从涵盖 57 个乳腺癌细胞系、1043 个原发性乳腺癌肿瘤和 99 个正常乳腺组织的 RNA-Seq 数据存储库中获取了 NAT1、NAT2 和 ESR1 的表达数据。使用非参数统计分析评估了基因表达之间以及乳腺癌细胞系中 NAT1 活性与 RNA 表达之间的关系。确定了每个数据集的基因表达差异，以及与原发性乳腺癌肿瘤相比正常乳腺组织中的基因表达差异，以及根据雌激素受体状态进行分层。在正常和原发性乳腺癌组织中检测到 NAT1 和 NAT2 mRNA 表达；NAT1 表达明显高于 NAT2。NAT1 和 ESR1 表达强烈相关，而 NAT2 和 ESR1 表达不相关。尽管 NAT1 和 NAT2 表达相关，但程度适中。与正常乳腺组织相比，原发性乳腺癌肿瘤组织中 NAT1、NAT2 和 ESR1 的表达增加；然而，NAT2 的差异幅度和显著性较低。对正常和原发性乳腺组织以及乳腺癌细胞系中的 NAT1、NAT2 和 ESR1 表达进行分析表明，NAT1 和 NAT2 的表达受不同机制的调节，而 NAT1 和 ESR1 的表达可能具有重叠的调节。定义这些关系对于未来的乳腺癌预防研究很重要。
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