Wang Qiuyu, Fang Wen-Hui, Krupinski Jerzy, Kumar Shant, Slevin Mark, Kumar Patricia
School of Biology, Chemistry and Health Science, Manchester Metropolitan University, and Department of Pathology Sciences, Christie Hospital, Manchester, United Kingdom.
J Cell Mol Med. 2008 Dec;12(6A):2281-94. doi: 10.1111/j.1582-4934.2008.00427.x. Epub 2008 Jul 4.
The paired box genes are a family of nine developmental control genes, which in human beings (PAX) and mice (Pax) encode nuclear transcription factors. The temporal and spatial expressions of these highly conserved genes are tightly regulated during foetal development including organogenesis. PAX/Pax genes are switched off during the terminal differentiation of most structures. Specific mutations within a number of PAX/Pax genes lead to developmental abnormalities in both human beings and mice. Mutation in PAX3 causes Waardenburg syndrome, and craniofacial-deafness-hand syndrome. The Splotch phenotype in mouse exhibits defects in neural crest derivatives such as, pigment cells, sympathetic ganglia and cardiac neural crest-derived structures. The PAX family also plays key roles in several human malignancies. In particular, PAX3 is involved in rhabdomyosarcoma and tumours of neural crest origin, including melanoma and neuroblastoma. This review critically evaluates the roles of PAX/Pax in oncogenesis. It especially highlights recent advances in knowledge of how their genetic alterations directly interfere in the transcriptional networks that regulate cell differentiation, proliferation, migration and survival and may contribute to oncogenesis.
成对盒基因是一个由九个发育控制基因组成的家族，在人类（PAX）和小鼠（Pax）中编码核转录因子。这些高度保守的基因在胎儿发育（包括器官发生）过程中的时空表达受到严格调控。PAX/Pax基因在大多数结构的终末分化过程中关闭。许多PAX/Pax基因内的特定突变会导致人类和小鼠出现发育异常。PAX3突变会导致瓦登伯革氏综合征以及颅面-耳聋-手综合征。小鼠中的斑点表型在神经嵴衍生物中表现出缺陷，如色素细胞、交感神经节和心脏神经嵴衍生结构。PAX家族在几种人类恶性肿瘤中也起着关键作用。特别是，PAX3参与横纹肌肉瘤以及神经嵴起源的肿瘤，包括黑色素瘤和神经母细胞瘤。本综述批判性地评估了PAX/Pax在肿瘤发生中的作用。它特别强调了最近在了解其基因改变如何直接干扰调节细胞分化、增殖、迁移和存活的转录网络以及可能如何导致肿瘤发生方面取得的进展。
