p53(V)蛋白在不同肿瘤组织中的表达

niwanmao

见文末的附图，分别是：
1例乳腺癌患者，p53(V)表达率0.34％
1例卵巢癌患者，p53(V)表达率51.35％
1例肺癌患者手术前放疗、化疗后，p53(V)表达率99.87％。

关于p53及其异构体的综述，可参见nature上的一篇文章：http://www.nature.com/onc/journal/v23/n3/full/1206929a.html
其最后有这么一段话，概括了p53及其异构体的生物学作用及其在肿瘤发生中的作用：
p53异构体的生物学作用尚需继续研究明确，全长的p53一般在基因受到破坏应激时产生，而异构体似乎只与p53一起参与正常生理调节。在肿瘤细胞中，经常可检测到p53异构体增高，N端异构体的过表达可能会抑制野生型p53的作用。

The biological functions of p53 isoforms remain to be elucidated. In contrast to full-length p53, there is no evidence that any of the N- or C-terminal variants accumulate in response to genotoxic stress. Therefore, their functions are likely to be relevant to the involvement of p53 in controlling normal, physiological processes. In cells exposed to stress, the accumulated full-length form is by far the dominant isoform, and it is unlikely that the low levels of p53 variants can have a significant biological effect. However, in non-stressed cells, the levels of p53 variants may match and sometimes surpass those of full-length p53, thus exerting important regulatory effects. Therefore, future work should concentrate on the elucidation of the mechanism that selectively regulates the expression of each isoform (alternative splicing, use of alternative promoter and/or initiation codon, differential protein stabilization).

Another, unresolved question relates to the role of p53 variants in tumorigenesis. There is evidence that, in many tumour cell lines, various small forms of p53 are present at detectable levels. However, the exact identity of these forms is not known. Overexpression of a N isoform may potentially inhibit wild-type p53 function in tumour cells that conserve wild-type alleles. Moreover, the effect of a mutation in the DNA-binding domain on the activity of the N- and C-terminal isoforms is still a matter of speculation. Further studies are needed to investigate the expression of specific p53 isoforms in primary tumours and to analyse the interactions between the various family members during tumour progression.

p53(V)蛋白在不同肿瘤组织中的表达