Chapman Emma J, Knowles Margaret A
Cancer Research UK Clinical Centre, Section of Experimental Oncology, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, United Kingdom.
Mol Carcinog. 2009 Nov;48(11):975-81. doi: 10.1002/mc.20567.
Necdin (NDN), a member of the melanoma-associated antigen (MAGE) family of proteins was first identified in mouse stem cells of embryonal carcinoma origin induced to differentiate by treatment with retinoic acid. The human gene maps to chromosome 15q11. This imprinted region is implicated in the pathogenesis of Prader-Willi syndrome (PWS), a neurodevelopmental disorder, where NDN is one of multiple genes silenced by deletion, maternal uniparental disomy or translocation. Due to this association, much interest has focused on the role of NDN in neuronal development and differentiation. However, a considerable number of studies have identified additional functions of NDN. Taken together these studies suggest a pleiotropic protein with diverse functions some of which may be relevant to tumorigenesis. Downregulation of NDN occurs in carcinoma cell lines and primary tumors, suggesting a tumor suppressor role. Our working hypothesis is that NDN is a worthy candidate for further studies with regard to a potential tumor suppressor role. In this article we outline the considerable evidence supporting the hypothesis that NDN has multiple functions, some of which indicate that it could be a tumor suppressor. The roles of NDN in key processes such as interaction with p53 and E2F-1, hematopoietic stem cell quiescence, transcriptional repression, angiogenesis, differentiation and interaction with the polycomb group gene BMI1 are discussed. Confirmation of NDN as a tumor suppressor may have implications for monitoring of PWS patients and could present a novel cancer therapeutic target.
神经生长抑制因子（Necdin，NDN）是黑色素瘤相关抗原（MAGE）蛋白家族的成员之一，最初是在源自胚胎癌的小鼠干细胞中发现的，这些干细胞在用视黄酸处理后被诱导分化。人类基因定位于染色体15q11。这个印记区域与普拉德-威利综合征（PWS）的发病机制有关，PWS是一种神经发育障碍，其中NDN是因缺失、母源单亲二体或易位而沉默的多个基因之一。由于这种关联，人们对NDN在神经元发育和分化中的作用产生了浓厚兴趣。然而，大量研究已经确定了NDN的其他功能。综合这些研究表明，NDN是一种具有多种功能的多效性蛋白，其中一些功能可能与肿瘤发生有关。NDN在癌细胞系和原发性肿瘤中表达下调，提示其具有肿瘤抑制作用。我们的工作假设是，就潜在的肿瘤抑制作用而言，NDN是值得进一步研究的候选对象。在本文中，我们概述了支持NDN具有多种功能这一假设的大量证据，其中一些证据表明它可能是一种肿瘤抑制因子。我们还讨论了NDN在与p53和E2F-1相互作用、造血干细胞静止、转录抑制、血管生成、分化以及与多梳蛋白家族基因BMI1相互作用等关键过程中的作用。确认NDN为肿瘤抑制因子可能对监测PWS患者有影响，并可能成为一种新的癌症治疗靶点。
