Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation
Temporally regulated neural crest transcription factors distinguish neuroectodermal tumors of varying malignancy and differentiation
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DOI：
10.1593/neo.04637
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发表时间：
2005-06-01
期刊：
影响因子：
4.8
通讯作者：
Gerald, WL
中科院分区：
文献类型：
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作者：
Gershon, TR;Oppenheimer, O;Gerald, WL
神经外胚层肿瘤细胞与神经嵴 (NC) 细胞一样，具有多能性、增殖性和迁移性。我们测试了这样的假设：NC 发育所必需的遗传程序在神经外胚层肿瘤中被激活。我们检测了转录因子 PAX3、PAX7、AP-2 α 和 SOX10 在人类胚胎和神经外胚层肿瘤中的表达：神经纤维瘤、神经鞘瘤、神经母细胞瘤、恶性神经鞘瘤、黑色素瘤、髓母细胞瘤、幕上原始神经外胚层肿瘤和尤文氏肉瘤。我们还分别检测了 SOX10、AP-2 α 和 PAX3 的靶标 1130、ERBB3 和 STX 的表达。 PAX3、AP-2α和SOX10在人类NC发育中依次表达，而PAX7仅限于中胚层。肿瘤以特定组合表达 PAX3、AP-2 α、SOX10 和 PAX7。 SOX10和AP-2α在相对分化的肿瘤中表达。早期NC标志物PAX3及其同源物PAX7在低分化肿瘤和具有恶性潜能的肿瘤中被检测到。 NC转录因子和靶基因的表达相关。因此，神经外胚层肿瘤中存在对 NC 发育至关重要的转录因子。特定 NC 转录因子与表型以及特定下游基因表达的相关性提供了这些转录因子积极影响基因表达和肿瘤行为的证据。这些发现表明 PAX3、PAX7、AP-2 α 和 SOX10 是潜在的预后标志物和治疗干预的目标。
Neuroectodermal tumor cells, like neural crest (NC) cells, are pluripotent, proliferative, and migratory. We tested the hypothesis that genetic programs essential to NC development are activated in neuroectodermal tumors. We examined the expression of transcription factors PAX3, PAX7, AP-2 alpha, and SOX10 in human embryos and neuroectodermal tumors: neurofibroma, schwannoma, neuroblastoma, malignant nerve sheath tumor, melanoma, medulloblastoma, supratentorial primitive neuroectodermal tumor, and Ewing's sarcoma. We also examined the expression of 1130, ERBB3, and STX, targets of SOX10, AP-2 alpha, and PAX3, respectively. PAX3, AP-2 alpha, and SOX10 were expressed sequentially in human NC development, whereas PAX7 was restricted to mesoderm. Tumors expressed PAX3, AP-2 alpha, SOX10, and PAX7 in specific combinations. SOX10 and AP-2 alpha were expressed in relatively differentiated neoplasms. The early NC marker, PAX3, and its homologue, PAX7, were detected in poorly differentiated tumors and tumors with malignant potential. Expression of NC transcription factors and target genes correlated. Transcription factors essential to NC development are thus present in neuroectodermal tumors. Correlation of specific NC transcription factors with phenotype, and with expression of specific downstream genes, provides evidence that these transcription factors actively influence gene expression and tumor behavior. These findings suggest that PAX3, PAX7, AP-2 alpha, and SOX10 are potential markers of prognosis and targets for therapeutic intervention.