文章：

神经系统的肿瘤抑制功能

Tumour-suppressor function in the nervous system

原文发布日期：2004-03-01

DOI: 10.1038/nrc1297

类型: Review Article

开放获取: 否

要点：

1. Tumour-suppressor genes probably evolved to perform specific functions related to development and homeostasis rather than to prevent cancer. Loss of tumour-suppressor function therefore contributes to cancer in some contexts, but leads to pathophysiological states that are distinct from cancer in other contexts.
2. The nervous system provides several examples of the differential effects of loss of tumour-suppressor function. This is related to the fact that it contains several different cell types, which, especially during development, reflect a wide range of proliferation and differentiation statuses.
3. Loss of function of the retinoblastoma protein (RB) in the nervous system causes increased proliferation in some situations and increased apoptosis in others. RB deficiency also influences differentiation in specific cell populations. This context-dependent activity probably contributes to the limited spectrum of tumours that is observed in families with germline RB mutations.
4. The tumour suppressor PTEN is involved in the control of growth, and another, ATM, has a key role in the response to DNA damage. However, mutations of these genes do not necessarily result in tumorigenesis in the nervous system, and can instead lead to distinct neuropathologies.
5. The outcome of disruption of tumour-suppressor signalling pathways is strongly influenced by the developmental stage and cell type in which a mutation occurs. Outcomes can be as varied as changes in cell size versus cell number, for example, due to mutation of PTEN, and cell death versus tumorigenesis, due to mutation of ATM and other components of DNA-damage-response pathways.
6. Loss of tumour-suppressor function might cause defects in surrounding cells that are secondary to the cell-autonomous abnormalities in mutant cells, such as defects in neurofibromatosis type 1 (NF1) function. The interplay between mutant cells and their environment contributes to cancer and to other pathological states in the nervous system.
7. Understanding tumour-suppressor function in different settings is crucial for understanding the complex, multifunctional roles of these key regulatory proteins, how their loss of function contributes to cancer, and how aberrant signals in cancer cells might be modulated to result in outcomes other than cancer.

要点翻译：

1. 抑癌基因的进化可能旨在执行与发育和稳态相关的特定功能，而非预防癌症。因此，抑癌功能丧失在某些情况下会促进癌症发生，但在其他情境中则导致与癌症截然不同的病理生理状态。
2. 神经系统提供了多种体现抑癌功能丧失差异效应的案例。这与其包含多种细胞类型有关，特别是在发育过程中，这些细胞呈现出广泛的增殖和分化状态差异。
3. 视网膜母细胞瘤蛋白（RB）功能在神经系统中缺失时，在某些情境下会导致增殖增强，而在另一些情境下却引起凋亡增加。RB缺陷还会影响特定细胞群体的分化进程。这种背景依赖的活性可能是导致RB种系突变家族中观察到的肿瘤谱系受限的原因之一。
4. 抑癌基因PTEN参与生长调控，而ATM基因则在DNA损伤应答中起关键作用。然而，这些基因突变未必引起神经系统肿瘤发生，反而可能导致独特的神经病理学改变。
5. 抑癌信号通路破坏的结果深受突变发生时的发育阶段和细胞类型影响。其结果可呈现显著差异：例如PTEN突变可能导致细胞大小与数量的变化，而ATM及DNA损伤应答通路其他组分突变则可能引发细胞死亡与肿瘤生成的不同结局。
6. 抑癌功能丧失可能通过突变细胞的细胞自主性异常引发周边细胞缺陷（如1型神经纤维瘤病NF1功能缺陷），这些继发性效应同样重要。突变细胞与其微环境的相互作用共同促进了神经系统癌症及其他病理状态的发生。
7. 理解抑癌基因在不同情境中的功能，对于揭示这些关键调控蛋白的复杂多效性角色、阐明其功能缺失如何促癌，以及探索如何调控癌细胞异常信号通路以导向非癌化结局具有至关重要的意义。

英文摘要：

Tumour suppressors prevent cancer by regulating processes such as cell proliferation and survival. However, their functions are diverse, and are often related to the cell type and tissue context. Mutations of tumour-suppressor genes result in unique outcomes in the nervous system that contrast with their roles in other organs. This is closely related to the cell types in which mutations occur and the developmental stage of the tissues that are affected. How can studying the tissue-specific functions of tumour suppressors in the nervous system help us to understand signalling pathways that are relevant to cancer and what are the therapeutic implications of this?

摘要翻译： 

肿瘤抑制因子通过调控细胞增殖和存活等过程来阻止癌症发生，但其功能多样，且常与细胞类型和组织环境相关。抑癌基因突变在中枢神经系统产生的后果与其他器官截然不同，这与突变发生的细胞类型及受累组织的发育阶段密切相关。研究肿瘤抑制因子在神经系统中的组织特异性功能，如何帮助我们理解癌症相关的信号通路？其治疗意义又是什么？

原文链接：

Tumour-suppressor function in the nervous system