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Profiling of gene expression regulated by 17β-estradiol and tamoxifen in estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines

机译:雌激素受体阳性和雌激素受体阴性的人乳腺癌细胞系中17β-雌二醇和他莫昔芬调节的基因表达谱

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摘要

One area of great importance in breast cancer (BC) research is the study of gene expression regulated by both estrogenic and antiestrogenic agents. Although many studies have been performed in this area, most of them have only addressed the effects of 17β-estradiol (E2) and tamoxifen (TAM) on MCF7 cells. This study aimed to determine the effect of low doses of E2 and TAM on the expression levels of 84 key genes, which are commonly involved in breast carcinogenesis, in four BC cell lines differentially expressing estrogen receptor (ER) α and HER2 (MCF7, T47D, BT474, and SKBR3). The results allowed us to determine the expression patterns modulated by E2 and TAM in ERα+ and ERα− cell lines, as well as to identify differences in expression patterns. Although the MCF7 cell line is the most frequently used model to determine gene expression profiles in response to E2 and TAM, the changes in gene expression patterns identified in ERα+ and ERα− cell lines could reflect distinctive properties of these cells. Our results could provide important markers to be validated in BC patient samples, and subsequently used for predicting the outcome in ERα+ and ERα− tumors after TAM or hormonal therapy. Considering that BC is a molecularly heterogeneous disease, it is important to understand how well, and which cell lines, best model that diversity.
机译:在乳腺癌(BC)研究中最重要的领域之一是研究由雌激素和抗雌激素药物调节的基因表达。尽管已经在该领域进行了许多研究,但大多数研究仅涉及17β-雌二醇(E2)和他莫昔芬(TAM)对MCF7细胞的影响。这项研究旨在确定低剂量E2和TAM对四种差异表达雌激素受体(ER)α和HER2的BC细胞系中84个关键基因表达水平的影响,这些基因通常与乳腺癌的发生有关(MCF7,T47D ,BT474和SKBR3)。结果使我们能够确定由E2和TAM在ERα+和ERα-细胞系中调控的表达模式,以及鉴定表达模式的差异。尽管MCF7细胞系是确定E2和TAM响应基因表达谱的最常用模型,但在ERα+和ERα-细胞系中鉴定的基因表达模式的变化可能反映了这些细胞的独特特性。我们的结果可能提供重要的标志物,以在BC患者样本中进行验证,并随后用于预测TAM或激素治疗后ERα+和ERα-肿瘤的结果。考虑到BC是一种分子异质性疾病,重要的是要了解这种细胞的多样性如何以及能最好地模拟这种多样性。

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