文章：

PAX基因在癌症及其发展中的全景图

A PANorama of PAX genes in cancer and development

原文发布日期：2006-01-01

DOI: 10.1038/nrc1778

类型: Review Article

开放获取: 否

要点：

1. An emerging role for several paired box (Pax) genes during development is the prevention of terminal differentiation and maintenance of a progenitor cell state, while also inducing cell-lineage commitment.
2. The involvement of tumour-associated Pax gene expression in promoting cell proliferation and survival is consistent with in vitro observations of tumour cell death induced by Pax-gene knockdown.
3. Five Pax genes, representing subgroups II (PAX2, PAX5 and PAX8) and III (PAX3 and PAX7) of the four Pax family subgroups, are often expressed in a wide range of cancer types.
4. Rearrangements of four of these Pax genes, PAX3, PAX5, PAX7 and PAX8, are associated with characteristic chromosomal translocations that occur in specific tumours.
5. Pax genes in subgroups II and III confer cell motility, cell survival and self-sufficiency in growth signals, which are characteristics that favour tumour progression. Conversely, Pax genes in subgroups I (PAX1 and PAX9) and IV (PAX4 and PAX6) are either less often involved in cancer or their expression is indicative of favourable prognosis, as observed for PAX6 and PAX9.
6. The structural basis of the four subgroups is proposed to explain why Pax genes in subgroups II and III, which contain an octapeptide region and at least a partial homeodomain, are associated with more aggressive cancers, and why the members of subgroups I and IV, possessing only one of these domains, are linked to a favourable outcome.

要点翻译：

1. 数个配对盒（Pax）基因在发育过程中逐渐显现的一个作用是阻止终端分化并维持祖细胞状态，同时诱导细胞谱系定向。
2. 肿瘤相关Pax基因表达促进细胞增殖和存活的作用，与通过Pax基因敲低诱导肿瘤细胞死亡的体外观察结果一致。
3. 代表四个Pax家族亚群中第二亚组（PAX2、PAX5和PAX8）和第三亚组（PAX3和PAX7）的五个Pax基因，常在多种癌症类型中表达。
4. 其中四个Pax基因（PAX3、PAX5、PAX7和PAX8）的重排与特定肿瘤中发生的特征性染色体易位相关。
5. 第二和第三亚组的Pax基因赋予细胞运动性、细胞存活能力及生长信号自给性，这些特性有利于肿瘤进展。相反，第一亚组（PAX1和PAX9）和第四亚组（PAX4和PAX6）的Pax基因较少参与癌症，或其表达提示良好预后（如PAX6和PAX9所示）。
6. 基于四个亚组的结构差异可以解释：为何含有八肽区域和至少部分同源结构域的第二、三亚组Pax基因与侵袭性更强的癌症相关，而仅拥有其中一个结构域的第一、四亚组成员则与良好预后相关。

英文摘要：

Populations of self-renewing cells that arise during normal embryonic development harbour the potential for rapid proliferation, migration or transdifferentiation and, therefore, tumour generation. So, control mechanisms are essential to prevent rapidly expanding populations from malignant growth. Transcription factors have crucial roles in ensuring establishment of such regulation, with the Pax gene family prominent amongst these. This review examines the role of Pax family members during embryogenesis, and their contribution to tumorigenesis when subverted.

摘要翻译： 

在胚胎正常发育过程中出现的自我更新细胞群体，具有快速增殖、迁移或转分化的潜力，因此也可能导致肿瘤的发生。因此，必须存在调控机制以防止这些快速扩增的细胞群体发生恶性生长。转录因子在建立这种调控中起着关键作用，其中Pax基因家族尤为突出。本文综述了Pax家族成员在胚胎发生中的作用，以及当其功能被异常利用时对肿瘤发生的贡献。

原文链接：

A PANorama of PAX genes in cancer and development