van Limpt Vera, Chan Alvin, Schramm Alexander, Eggert Angelika, Versteeg Rogier
Department of Human Genetics, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.
Cancer Lett. 2005 Oct 18;228(1-2):59-63. doi: 10.1016/j.canlet.2005.02.050.
We recently identified six neuroblastoma patients with constitutional or tumor-specific mutations in the homeobox gene Phox2B. Phox2B controls part of the differentiation program of the sympathetic nervous system (SNS). Mice with a homozygous inactivation of Phox2B fail in the proper differentiation of the chromaffin lineage of the SNS. Phox2B regulates HASH1 which can control expression of genes of the Delta-Notch pathway. We previously showed that a subset of neuroblastoma cell lines highly expresses Delta-like 1 (Dlk1), which is a marker for the chromaffin lineage of the SNS. Notch3 is expressed in another subset of neuroblastoma cell lines and marks tumors from an alternative differentiation lineage. Phox2B is also related to the TrkA differentiation pathway in neuroblastoma. Here we will review the role of Phox2B in differentiation programs of the SNS and in neuroblastoma pathogenesis.
我们最近鉴定出6名患有同源框基因Phox2B的先天性或肿瘤特异性突变的神经母细胞瘤患者。Phox2B控制交感神经系统（SNS）分化程序的一部分。Phox2B纯合失活的小鼠在SNS嗜铬细胞谱系的正常分化中失败。Phox2B调节HASH1，HASH1可控制Delta-Notch信号通路基因的表达。我们之前表明，一部分神经母细胞瘤细胞系高表达Delta样1（Dlk1），Dlk1是SNS嗜铬细胞谱系的标志物。Notch3在另一部分神经母细胞瘤细胞系中表达，并标记来自另一种分化谱系的肿瘤。Phox2B也与神经母细胞瘤中的TrkA分化途径有关。在此，我们将综述Phox2B在SNS分化程序和神经母细胞瘤发病机制中的作用。
