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17β-雌二醇和他莫昔芬对雌激素受体阳性和雌激素受体阴性人乳腺癌细胞系中基因表达的调控分析

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

作者信息

Rangel Nelson, Villegas Victoria E, Rondón-Lagos Milena

机构信息

Department of Medical Sciences, University of Turin, Turin, Italy.

Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá, Colombia.

出版信息

Breast Cancer (Dove Med Press). 2017 Sep 20;9:537-550. doi: 10.2147/BCTT.S146247. eCollection 2017.

Abstract

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.

摘要

乳腺癌(BC)研究中一个非常重要的领域是对受雌激素和抗雌激素药物调节的基因表达的研究。尽管该领域已经开展了许多研究,但大多数研究仅探讨了17β-雌二醇(E2)和他莫昔芬(TAM)对MCF7细胞的影响。本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(MCF7、T47D、BT474和SKBR3)中84个通常参与乳腺癌发生的关键基因表达水平的影响。研究结果使我们能够确定E2和TAM在ERα+和ERα-细胞系中调节的表达模式,以及识别表达模式的差异。尽管MCF7细胞系是用于确定E2和TAM响应中基因表达谱最常用的模型,但在ERα+和ERα-细胞系中鉴定出的基因表达模式变化可能反映了这些细胞的独特特性。我们的研究结果可为在BC患者样本中验证的重要标志物提供依据,并随后用于预测TAM或激素治疗后ERα+和ERα-肿瘤的预后。鉴于BC是一种分子异质性疾病,了解哪种细胞系能最好地模拟这种多样性以及模拟得有多好非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c35/5614746/1ec664bb23b2/bctt-9-537Fig1.jpg

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