Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development
Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development
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Phox2B 与 MYCN 相关，是神经母细胞瘤发展的预后标志物。
DOI：
10.3892/ol.2015.3088
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发表时间：
2015-06-01
期刊：
影响因子：
2.9
通讯作者：
Cui, Hongjuan
中科院分区：
文献类型：
--
作者：
Ke, Xiao-Xue;Zhang, Dunke;Cui, Hongjuan
神经母细胞瘤是儿童最常见的颅外恶性肿瘤之一，约占儿童肿瘤相关死亡的15%。一般认为，神经母细胞瘤起源于椎旁交感神经节和肾上腺髓质中的神经脊细胞。然而，神经母细胞瘤在交感神经发生过程中发生的机制以及驱动神经母细胞瘤发展的细胞机制仍不清楚。本研究在人神经母细胞瘤转基因小鼠模型TH-MYCN小鼠模型中，研究了酪氨酸羟基酶-nu-myc禽髓细胞瘤病毒型原癌基因衍生神经母细胞瘤小鼠模型中神经母细胞瘤发育过程中的细胞成分。目前的研究表明，成对的类同源盒2b(PHOX2B)(+)神经前体细胞是增生性皮损和原发肿瘤的主要细胞群。此外，在增生性病变或原发肿瘤中，PHOX2B(+)神经前体细胞处于活跃的增殖和未分化状态。目前的研究还表明，PHOX2B的高表达水平促进了神经母细胞瘤细胞的增殖和异种移植瘤的生长。这些结果表明，未分化的PHOX2B(+)神经前体细胞的增殖是促进神经母细胞瘤发生发展的细胞机制，提示PHOX2B在神经母细胞瘤的发病机制中起着关键的调节作用。
Neuroblastoma is the one of the most common extracranial childhood malignancies, accounting for similar to 15% of tumor-associated deaths in children. It is generally considered that neuroblastoma originates from neural crest cells in the paravertebral sympathetic ganglia and the adrenal medulla. However, the mechanism by which neuroblastoma arises during sympathetic neurogenesis and the cellular mechanism that drives neuroblastoma development remains unclear. The present study investigated the cell components during neuroblastoma development in the tyrosine hydroxylase-nu-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (TH-MYCN) mouse model, a transgenic mouse model of human neuroblastoma. The present study demonstrates that paired-like homeobox 2b (Phox2B)(+) neuronal progenitors are the major cellular population in hyperplastic lesions and primary tumors. In addition, Phox2B(+) neuronal progenitors in hyperplastic lesions or primary tumors were observed to be in an actively proliferative and undifferentiated state. The current study also demonstrated that high expression levels of Phox2B promotes neuroblastoma cell proliferation and xenograft tumor growth. These findings indicate that the proliferation of undifferentiated Phox2B(+) neuronal progenitors is a cellular mechanism that promotes neuroblastoma development and.indicates that Phox2B is a critical regulator in neuroblastoma pathogenesis.