文章：

视网膜母细胞瘤基因抑制肿瘤的细胞机制

Cellular mechanisms of tumour suppression by the retinoblastoma gene

原文发布日期：2008-07-24

DOI: 10.1038/nrc2399

类型: Review Article

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要点：

1. RB, the retinoblastoma protein, has been identified as a crucial tumour suppressor. It is believed to be directly or indirectly inactivated in nearly all human cancers.
2. RB has been demonstrated to bind to over one hundred protein partners and has been shown to mediate transcriptional regulation of hundreds of target genes. These protein partners and transcriptional targets are thought to mediate the numerous cellular functions of RB, including temporary and permanent cell cycle arrest, genomic stability, apoptosis and differentiation.
3. The cellular functions of RB, as well as a potential role in angiogenesis and metastasis, might contribute to its role as a tumour suppressor, but it is currently unknown which function is most critical. Distinct cellular functions of RB might contribute to its role in preventing tumour initiation versus its role in preventing tumour progression.
4. The function of RB that is crucial for tumour suppression might also depend on in which type of cell RB is lost — stem cell, progenitor or differentiated cell — as well as in which tissue.
5. In some contexts, presence of RB during earlier stages might be beneficial to tumour progression. Effects of post-translational modifications of RB on individual cellular functions might contribute to preference for a tumour to mutate RB or an upstream regulator.

要点翻译：

1. 视网膜母细胞瘤蛋白（RB蛋白）已被确定为关键的肿瘤抑制因子。据信在几乎所有人类癌症中，该蛋白都会直接或间接失活。
2. 研究证实RB蛋白可与上百种蛋白质伴侣结合，并能介导数百个靶基因的转录调控。这些蛋白质伴侣和转录靶标被认为介导了RB蛋白的多种细胞功能，包括暂时性与永久性细胞周期阻滞、基因组稳定性调控、细胞凋亡和分化。
3. RB蛋白的细胞功能及其在血管生成和转移中的潜在作用，共同构成了其肿瘤抑制功能的基础，但目前尚不清楚哪种功能最为关键。RB蛋白在抑制肿瘤发生与阻止肿瘤进展两个阶段可能通过不同的细胞功能发挥作用。
4. RB蛋白抑癌功能的关键环节可能还取决于其所缺失的细胞类型（干细胞、祖细胞或分化细胞）以及所在的组织环境。
5. 在某些情况下，早期阶段RB蛋白的存在可能反而有利于肿瘤进展。RB蛋白翻译后修饰对特定细胞功能的影响，可能导致肿瘤更倾向于突变RB基因或其上游调控因子。

英文摘要：

The retinoblastoma (RB) tumour suppressor gene is functionally inactivated in a broad range of paediatric and adult cancers, and a plethora of cellular functions and partners have been identified for the RB protein. Data from human tumours and studies from mouse models indicate that loss of RB function contributes to both cancer initiation and progression. However, we still do not know the identity of the cell types in which RB normally prevents cancer initiation in vivo, and the specific functions of RB that suppress distinct aspects of the tumorigenic process are poorly understood.

摘要翻译： 

视网膜母细胞瘤（RB）抑癌基因在多种儿童及成人癌症中均发生功能性失活，RB蛋白已被发现具有大量细胞功能及相互作用伙伴。人类肿瘤数据和小鼠模型研究表明，RB功能的丧失既促进癌症的发生，也加速其进展。然而，我们仍不清楚RB在体内通常于哪些细胞类型中阻止癌症起始，亦不了解RB在抑制肿瘤过程不同环节中所发挥的具体功能。

原文链接：

Cellular mechanisms of tumour suppression by the retinoblastoma gene