Expression of HOXC9 and E2F2 are up-regulated in CD133+ cells isolated from human astrocytomas and associate with transformation of human astrocytes

Oswaldo K. Okamoto , Sueli M. Oba-Shinjo , Luciana Lopes , Suely K. Nagahashi Marie
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引用次数: 43

Abstract

Comparative analysis of cancer stem cells with their neoplastic and non-neoplastic counterparts should help better understand the underlying molecular events leading to transformation and tumor dissemination. Here, we report a molecular signature comprised by genes with exclusive aberrant expression in CD133+ cells, a reported subpopulation of tumorigenic stem-like cells, isolated from human glioblastomas. Microarrays covering 55,000 transcripts were used to compare gene expression profiles in purified subpopulations of CD133+ and CD133− GBM cells. Sixteen genes, many of which not previously associated with astrocytomas, were found aberrantly expressed in CD133+ cells, but not in CD133−, when compared with corresponding non-neoplastic controls. Up-regulation of two of such genes, E2F2 and HOXC9, was detected in a set of 54 astrocytomas of different grades and significantly associated with malignancy. Due to their distinctive expression in CD133+ cells, the use of E2F2 and HOXC9 as therapeutic targets for tumor eradication is suggested.

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HOXC9和E2F2在人星形细胞瘤分离的CD133+细胞中表达上调,并与人星形细胞的转化有关
对肿瘤干细胞和非肿瘤干细胞进行比较分析,有助于更好地了解导致转化和肿瘤传播的潜在分子事件。在这里,我们报告了CD133+细胞中具有独家异常表达的基因组成的分子特征,CD133+细胞是报道的从人胶质母细胞瘤中分离出来的致瘤性干细胞样细胞亚群。使用覆盖55,000个转录本的微阵列来比较纯化的CD133+和CD133−GBM细胞亚群中的基因表达谱。与相应的非肿瘤对照相比,16个基因(其中许多先前与星形细胞瘤无关)在CD133+细胞中异常表达,而在CD133−细胞中没有异常表达。在54例不同级别的星形细胞瘤中检测到E2F2和HOXC9这两个基因的上调,并与恶性肿瘤显著相关。由于E2F2和HOXC9在CD133+细胞中的独特表达,建议使用它们作为肿瘤根除的治疗靶点。
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