Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development

Ke,Xiao‑Xue; Zhang,Dunke; Zhao,Hailong; Hu,Renjian; Dong,Zhen; Yang,Rui; Zhu,Shunqin; Xia,Qingyou; Ding,Han‑Fei; Cui,Hongjuan

doi:10.3892/ol.2015.3088

Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma development

Authors:
- Xiao‑Xue Ke
- Dunke Zhang
- Hailong Zhao
- Renjian Hu
- Zhen Dong
- Rui Yang
- Shunqin Zhu
- Qingyou Xia
- Han‑Fei Ding
- Hongjuan Cui
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Affiliations: Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, P.R. China, Department of Pharmaceutical Engineering, School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400050, P.R. China, Department of Biochemistry and Molecular Biology, Cancer Center, Medical College of Georgia, Georgia Regents University, Augusta, GA 30912, USA
Published online on: March 31, 2015 https://doi.org/10.3892/ol.2015.3088
Pages: 2507-2514
Copyright: © Ke et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuroblastoma is the one of the most common extracranial childhood malignancies, accounting for ~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‑v‑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.

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