Homeobox Transcription Factor Prox1 in Sympathetic Ganglia of Vertebrate Embryos: Correlation With Human Stage 4s Neuroblastoma
Homeobox Transcription Factor Prox1 in Sympathetic Ganglia of Vertebrate Embryos: Correlation With Human Stage 4s Neuroblastoma
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DOI：
10.1203/00006450-201011001-00215
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发表时间：
2010-08-01
影响因子：
3.6
通讯作者：
Wilting, Joerg
中科院分区：
文献类型：
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作者：
Becker, Juergen;Wang, Baigang;Wilting, Joerg
以前，我们观察到的同源异型盒转录因子Prox 1在神经外胚层胚胎组织的表达。除了在胚胎发育过程中的基本功能外，Prox 1还涉及恶性肿瘤的进展和抑制。在这里，我们表明，Prox 1表达在胚胎交感神经干神经节的鸟类和小鼠胚胎。Prox 1蛋白定位于神经递质阳性交感神经元的核中。交感神经祖细胞代表神经母细胞瘤（NB）的起源细胞，NB是儿童最常见的颅外恶性肿瘤。NB可进展至危及生命的第4期，或在特殊的第4期自发消退。通过qRT-PCR，我们发现，Prox I在24个人NB细胞系中的表达水平较低，与人淋巴管内皮细胞（LEC）相比，而在胚胎LEC和交感神经元中可以看到相等的细胞核免疫染色。在NB第1、2、3和4期中，我们观察到几乎相同的表达水平，但在第4期NB中表达量显着更高。通过免疫组化，我们发现变量的Prox 1蛋白在NB细胞的细胞核中，显示内部和个体间的差异。由于阶段4S NB容易发生出生后细胞凋亡，我们假设高Prox 1水平对其行为至关重要。（Pediatr Res 68：112-117，2010）
Previously, we observed expression of the homeobox transcription factor Prox1 in neuroectodermal embryonic tissues. Besides essential functions during embryonic development, Prox1 has been implicated in both progression and suppression of malignancies. Here, we show that Prox1 is expressed in embryonic sympathetic trunk ganglia of avian and murine embryos. Prox1 protein is localized in the nucleus of neurofilament-positive sympathetic neurons. Sympathetic progenitors represent the cell of origin of neuroblastoma (NB), the most frequent solid extracranial malignancy of children. NB may progress to life-threatening stage 4, or regress spontaneously in the special stage 4s. By qRT-PCR, we show that Prox I is expressed at low levels in 24 human NB cell lines compared with human lymphatic endothelial cells (LECs), whereas equal immunostaining of nuclei can be seen in embryonic LECs and sympathetic neurons. In NB stages 1, 2, 3, and 4, we observed almost equal expression levels, but significantly higher amounts in stage 4s NB. By immunohistochemistry, we found variable amounts of Prox 1 protein in nuclei of NB cells, showing intra and interindividual differences. Because stage 4s NB are susceptible to postnatal apoptosis, we assume that high Prox1 levels are critical for their behavior. (Pediatr Res 68: 112-117, 2010)