Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cell Cycle. 2010 Jun 15;9(12):2434-41. doi: 10.4161/cc.9.12.12051.
The phenotypes of the p63 mutant mice are complex and diverse. The p63-/- mice develop severe defects in morphogenesis of ectodermal appendages, and p63+/- mice are tumor prone. Transcriptional targets of p63 with functions in both of these biological processes likely exist. Here, we identified one such direct transcriptional target of p63, brachyury, a gene with diverse roles in limb development and tumorigenesis. We found that brachyury is not expressed in developing p63-/- mouse embryos, and that in osteosarcomas, ΔNp63 and brachyury are expressed at high levels. Knock down of ΔNp63 in tumor cells resulted in a concomitant diminution of brachyury, cell proliferation, migration and invasion. These data provide evidence that suppression of ΔNp63 in tumors may lead to tumor regression through loss of cell proliferative and metastatic potential.
p63 突变小鼠的表型复杂多样。p63-/- 小鼠在外胚层附肢的形态发生中出现严重缺陷，而 p63+/- 小鼠易发生肿瘤。p63 在这两个生物学过程中具有功能的转录靶标可能存在。在这里，我们鉴定了 p63 的一个这样的直接转录靶标，即 brachyury，它在肢体发育和肿瘤发生中具有多种作用的基因。我们发现 brachyury 在发育中的 p63-/- 小鼠胚胎中不表达，并且在骨肉瘤中，ΔNp63 和 brachyury 高表达。在肿瘤细胞中敲低 ΔNp63 会导致 brachyury、细胞增殖、迁移和侵袭的同时减少。这些数据提供了证据，表明通过丧失细胞增殖和转移潜能，抑制肿瘤中的 ΔNp63 可能导致肿瘤消退。
