文章：

RUNX基因：癌症中功能的获得或丧失

The runx genes: gain or loss of function in cancer

原文发布日期：2005-04-20

DOI: 10.1038/nrc1607

类型: Review Article

开放获取: 否

要点：

1. The RUNX genes encode transcription factors that bind DNA as components of the core-binding factor (CBF) complex, in partnership with the CBFβ cofactor. This complex activates and represses transcription of key regulators of growth, survival and differentiation pathways.
2. The mouse RUNX genes are closely related and are essential for haematopoiesis, osteogenesis and neurogenesis, but are also important for other developmental processes.
3. The RUNX genes have been found to function as both tumour suppressors and dominant oncogenes in a context-dependent manner.
4. RUNX1 is a frequent target of chromosomal translocation in distinct subtypes of human leukaemia: RUNX1–ETO occurs in 10–20% of acute myeloid leukaemias and TEL–RUNX1 in 20–25% of childhood acute lymphoid leukaemias.
5. Functional disruption of RUNX1 by chromosomal translocation and somatic point mutation occurs commonly in myeloid leukaemia. RUNX1 mutations have also been linked with familial predisposition to acute leukaemia.
6. Hypermethylation of RUNX3 has been found in several human epithelial cancers and loss of Runx3 predisposes knockout mice to gastric hyperplasia, indicating a tumour-suppressor-like role for this gene.
7. All three RUNX genes are targets for retroviral insertional activation in mouse lymphoma models, and transgenic mice expressing full-length Runx2 develop T-cell lymphoma, confirming the oncogenic potential of this gene family.
8. Amplification of RUNX1 has been linked with poor prognosis in childhood B-cell leukaemia, while RUNX2 expression has been implicated in bone metastasis.
9. RUNX proteins are central to pathways regulating cell growth and differentiation. Of particular note are the interactions of RUNX activities with the transforming growth factor-β pathway.

要点翻译：

1. RUNX基因编码的转录因子作为核心结合因子（CBF）复合体的组成部分，与CBFβ辅因子协同结合DNA。该复合体能激活和抑制生长、存活及分化通路关键调控因子的转录。
2. 小鼠RUNX基因高度同源，对造血、成骨和神经发生至关重要，同时也参与其他发育过程。
3. 研究发现RUNX基因具有背景依赖性双重功能：既可充当肿瘤抑制因子，也能作为显性癌基因。
4. 在人类白血病不同亚型中，RUNX1是染色体易位的常见靶点：RUNX1–ETO易位见于10%-20%的急性髓系白血病，TEL–RUNX1易位见于20%-25%的儿童急性淋巴细胞白血病。
5. 染色体易位和体细胞点突变导致的RUNX1功能破坏常见于髓系白血病，该基因突变亦与家族性急性白血病易感性相关。
6. RUNX3基因高甲基化现象发现于多种人类上皮性肿瘤，Runx3基因敲除小鼠易发生胃增生，提示该基因的肿瘤抑制功能。
7. 小鼠淋巴瘤模型中，所有三种RUNX基因均为逆转录病毒插入激活的靶点；表达全长Runx2的转基因小鼠会发展为T细胞淋巴瘤，证实该基因家族具有致癌潜力。
8. RUNX1扩增与儿童B细胞白血病不良预后相关，而RUNX2表达则与骨转移有关。RUNX蛋白是调控细胞生长和分化通路的核心枢纽，尤其值得注意的是RUNX活性与转化生长因子-β通路的相互作用。

英文摘要：

The RUNX genes have come to prominence recently because of their roles as essential regulators of cell fate in development and their paradoxical effects in cancer, in which they can function either as tumour-suppressor genes or dominant oncogenes according to context. How can this family of transcription factors have such an ambiguous role in cancer? How and where do these genes impinge on the pathways that regulate growth control and differentiation? And what is the evidence for a wider role for the RUNX genes in non-haematopoietic cancers?

摘要翻译： 

RUNX基因因其在发育中作为细胞命运的关键调控因子，以及在癌症中表现出的矛盾作用——依据不同情境既可作为抑癌基因，也可作为显性癌基因——而近来备受关注。这一转录因子家族为何在癌症中扮演如此模棱两可的角色？它们又如何以及在何处影响调控生长与分化的信号通路？此外，RUNX基因在非血液系统肿瘤中是否发挥更广泛作用的证据又有哪些？

原文链接：

The runx genes: gain or loss of function in cancer