Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
Expression of the RNA helicase DDX3 and the hypoxia response in breast cancer.
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DOI：
10.1371/journal.pone.0063548
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
van Diest PJ
中科院分区：
文献类型：
--
作者：
Bol GM;Raman V;van der Groep P;Vermeulen JF;Patel AH;van der Wall E;van Diest PJ
DDX3是一种RNA解旋酶，具有抗细胞凋亡的特性，促进增殖和转化。此外，在乳腺癌细胞系中，DDX3被证明是HIF-1α(缺氧反应的主要调节因子)的直接下游靶点。然而，在人类肿瘤中，DDX3与缺氧的关系尚未得到解决。本文研究了DDX3基因与乳腺癌组织中缺氧反应蛋白的关系。采用免疫组织化学方法检测DX3在乳腺癌组织中的表达，并与缺氧相关蛋白HIF-1α、GLUT1、CAIX、EGFR、HER2、AKT1、FOXO4、P53、ERα、COMMD1、FER激酶、Pin1、E-钙粘素、p21、p27、转铁蛋白受体、FOXO3a、c-Met和Notch1进行比较。在366例乳腺癌患者中，有127例DDX3过表达，且与HIF-1α及其下游基因CAIx和GLUT1的过表达有关。此外，DDX3的表达与缺氧相关蛋白EGFR、HER2、FOXO4、ERα和c-Met呈正相关，与COMMD1、FER激酶、AKT1、E-钙粘蛋白、TfR和FOXO3a的表达不依赖于HIF-1α。在浸润性乳腺癌中，DDX3的表达与缺氧诱导因子-1α及其他缺氧相关蛋白的过表达相关，提示DDX3在缺氧条件下具有独特的作用，支持DDX3的致癌作用，这可能对目前DDX3抑制剂的开发具有临床意义。
DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. In addition, DDX3 was shown to be a direct downstream target of HIF-1α (the master regulatory of the hypoxia response) in breast cancer cell lines. However, the relation between DDX3 and hypoxia has not been addressed in human tumors. In this paper, we studied the relation between DDX3 and the hypoxic responsive proteins in human breast cancer. DDX3 expression was investigated by immunohistochemistry in breast cancer in comparison with hypoxia related proteins HIF-1α, GLUT1, CAIX, EGFR, HER2, Akt1, FOXO4, p53, ERα, COMMD1, FER kinase, PIN1, E-cadherin, p21, p27, Transferrin receptor, FOXO3A, c-Met and Notch1. DDX3 was overexpressed in 127 of 366 breast cancer patients, and was correlated with overexpression of HIF-1α and its downstream genes CAIX and GLUT1. Moreover, DDX3 expression correlated with hypoxia-related proteins EGFR, HER2, FOXO4, ERα and c-Met in a HIF-1α dependent fashion, and with COMMD1, FER kinase, Akt1, E-cadherin, TfR and FOXO3A independent of HIF-1α. In invasive breast cancer, expression of DDX3 was correlated with overexpression of HIF-1α and many other hypoxia related proteins, pointing to a distinct role for DDX3 under hypoxic conditions and supporting the oncogenic role of DDX3 which could have clinical implication for current development of DDX3 inhibitors.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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作者：
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