Mice lacking the p53/p63 target gene perp are resistant to papilloma development
Mice lacking the p53/p63 target gene perp are resistant to papilloma development
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DOI：
10.1158/0008-5472.can-05-0366
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发表时间：
2005-08-01
期刊：
影响因子：
11.2
通讯作者：
Attardi, LD
中科院分区：
文献类型：
--
作者：
Marques, MR;Horner, JS;Attardi, LD
PERP是参与DNA损伤诱导的细胞凋亡途径的P53肿瘤抑制因子的靶点。此外，在皮肤发育过程中，PERP是P53相关转录因子P63的靶标，参与通过桥粒介导的细胞间黏附。在这里，我们在一个两步皮肤癌模型系统中测试PERP在肿瘤发生中的作用。我们发现，皮肤中缺乏PERP的小鼠对乳头状瘤的发展具有抵抗力，表现出比野生型小鼠更少、更小的乳头状瘤。在经过处理的PERP缺陷小鼠和野生型小鼠的皮肤中，增殖水平、凋亡指数和分化模式相似。相反，通过异常桥粒组装造成的粘附性受损可能解释了在缺乏PERP的情况下肿瘤发展减少的原因。这些研究表明，在某些情况下，PERP是有效致癌所必需的，并表明在这些情况下，完整的细胞-细胞黏附在支持肿瘤发展中发挥了作用。
Perp is a target of the p53 tumor suppressor involved in the DNA damage-induced apoptosis pathway. In addition, Perp is a target of the p53-related transcription factor p63 during skin development, where it participates in cell-cell adhesion mediated through desmosomes. Here we test the role of Perp in tumorigenesis in a two-step skin carcinogenesis model system. We find that mice lacking Perp in the skin are resistant to papilloma development, displaying fewer and smaller papillomas than wild-type mice. Proliferation levels, apoptotic indices and differentiation patterns are similar in the skin of treated Perp-deficient and wild-type mice. Instead, impaired adhesion through aberrant desmosome assembly may explain the diminished tumor development in the absence of Perp. These studies indicate that in certain contexts, Perp is required for efficient carcinogenesis and suggest a role for intact cell-cell adhesion in supporting tumor development in these settings.