TP63 gene in stress response and carcinogenesis: a broader role than expected.
TP63 gene in stress response and carcinogenesis: a broader role than expected.
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TP63 基因在应激反应和致癌作用中：比预期更广泛的作用。
DOI：
10.1684/bdc.2006.0170
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发表时间：
2006
影响因子：
1.2
通讯作者：
C. Caron de Fromentel
中科院分区：
文献类型：
--
作者：
A. Petitjean;P. Hainaut;C. Caron de Fromentel
TP63基因是TP53基因家族的一员。与TP53不同的是，这种基因在癌症中并不经常因突变而失活。对TP63进行的初步实验表明，p63蛋白在上皮和间充质组织的分化和形态发生调控中起着重要作用。然而，越来越多的证据表明p63也通过多种机制参与了肿瘤的发生。事实上，TP63在约25%的肺、头颈和食道鳞状细胞癌中检测到扩增。这导致p63的截断形式（DeltaNp63）过表达，这可能抵消全长p63 （TAp63）以及其他家族成员p53和TAp73诱导的生长抑制。此外，TP63杂合的小鼠发生自发性肿瘤。尽管p53在对许多dna损伤因子的反应中起主要作用，但p63在这一过程中的参与并没有很好的文献记载。然而，最近有几个研究小组报道，TAp63可以单独或与化疗药物协同诱导dna损伤细胞的细胞周期阻滞和凋亡，从而作为一种化学敏感因子出现。总的来说，除了在分化和形态发生中具有非冗余的特异性功能外，p63似乎还发挥着与p53相似的生物学功能，并在肿瘤发生和抗癌治疗反应的调节中发挥着越来越重要的作用。
The TP63 gene is a member of the TP53 gene family. In contrast with TP53, this gene is not frequently inactivated by mutation in cancer. Initial experiments with disrupted TP63 have allowed specifying p63 protein a role in the regulation of differentiation and morphogenesis in epithelial and mesenchymal tissues. Nevertheless, there is growing evidence that p63 is also involved in oncogenesis through several mechanisms. Indeed, amplification of TP63 is detected in about 25% of squamous cell carcinomas of lung, head and neck and oesophagus. This results in overexpression of a truncated form of p63 (DeltaNp63) that may counteract growth suppression induced by full length p63 (TAp63), as well as by the other family members, p53 and TAp73. Moreover, mice heterozygous for TP63 develop spontaneous tumours. Whereas p53 plays a major role in response to numerous DNA-damaging agents, the involvement of p63 in this process is not well documented. Nevertheless, several groups recently reported that TAp63 can induce cell cycle arrest and apoptosis in DNA-damaged cells, alone or in synergy with chemotherapeutic agents, and thus appears as a chemosensitivity factor. Overall, in addition to non-redundant, specific functions in differentiation and morphogenesis, p63 appears to exert biological functions similar to those of p53 and to take a growing place in oncogenesis and modulation of responses to anti-cancer therapy.