Characterization of the expression of the hypoxia-induced genes neuritin, TXNIP and IGFBP3 in cancer
Characterization of the expression of the hypoxia-induced genes neuritin, TXNIP and IGFBP3 in cancer
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DOI：
10.1016/j.febslet.2006.05.011
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发表时间：
2006-06-12
期刊：
影响因子：
3.5
通讯作者：
Germain, Stéphane
中科院分区：
文献类型：
--
作者：
Le Jan, Sébastien;Le Meur, Nolwenn;Germain, Stéphane
通过触发对缺氧的适应性反应（这是肿瘤微环境的共同特征），内皮细胞促进了参与肿瘤生长的血管生成反应的发生。因此，识别低氧标志物对于更好地理解肿瘤血管生成和优化抗血管生成治疗策略是一个挑战。利用代表性差异分析结合微阵列，我们在此报告了133缺氧诱导的人微内皮细胞（HMEC-1）转录物的鉴定。通过Northern blot，我们证实了缺氧诱导胰岛素样生长因子结合蛋白3 （igfbp3）、硫氧还蛋白相互作用蛋白（txnip）和神经素（nrn1）的表达。最后，通过对几种类型的人类肿瘤进行原位杂交，我们提供了nrn1和txnip作为缺氧周围坏死标记物和igfbp3作为肿瘤内皮标记物的证据。我们认为这些缺氧诱导的基因可以代表癌症治疗干预的相关预后工具和靶点。(c) 2006年欧洲生化学会联合会。Elsevier B.V.版权所有。
By triggering an adaptive response to hypoxia which is a common feature of tumor microenvironments, endothelial cells contribute to the onset of angiogenic responses involved in tumor growth. Therefore, identifying hypoxic markers represent a challenge for a better understanding of tumor angiogenesis and for the optimization of anti-angiogenic therapeutic strategy. Using representational difference analysis combined with microarray, we here report the identification of 133 hypoxia-induced transcripts in human microendothelial cells (HMEC-1). By Northern blot, we confirm hypoxia-induced expression of insulin-like growth factor binding protein 3 (igfbp3), thioredoxin-interacting protein (txnip), neuritin (nrn1). Finally, by performing in situ hybridization on several types of human tumors, we provide evidence for nrn1 and txnip as hypoxic perinecrotic markers and for igfbp3 as a tumor endothelial marker. We propose these hypoxia-induced genes could represent relevant prognostic tools and targets for therapeutic intervention in cancers. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.