Hagiwara K, McMenamin M G, Miura K, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Cancer Res. 1999 Sep 1;59(17):4165-9.
After the identification of p73, a second homologue of the human p53 tumor suppressor gene has been reported and named p63/p73L/p51/p40/CUSP/KET. We have investigated the hypotheses that: (a) p63 is mutated in diverse types of human cancers; and (b) p63 functions in the same pathway as p53 and p73 in the process of carcinogenesis; therefore, mutations in these three genes would be mutually exclusive. We have analyzed the genomic structure of the p63 gene and have performed mutational analyses on 54 human cell lines using intronic primers flanking each exon. We have confirmed that the human p63 open reading frame encodes the same length of protein as murine p63 that was initially reported to be 39 amino acids longer than human p63. By mutational analysis, we have shown that DLD1 and SKOV3 cells have either heterozygous mutations or polymorphisms in the putative DNA binding domain of p63. In these cell lines, p63 is biallelically expressed. We conclude that mutations in the p63 gene are rare in human cell lines. The fact that DLD1 is abnormal for both p63 and p53 genes suggests that they may not be involved in the same tumor suppressor pathway.
在p73被鉴定出来后，人类p53肿瘤抑制基因的第二个同源物被报道，并被命名为p63/p73L/p51/p40/CUSP/KET。我们研究了以下假设：(a) p63在多种类型的人类癌症中发生突变；(b) p63在致癌过程中与p53和p73在同一途径中发挥作用；因此，这三个基因的突变将是相互排斥的。我们分析了p63基因的基因组结构，并使用位于每个外显子两侧的内含子引物对54个人类细胞系进行了突变分析。我们已经证实，人类p63开放阅读框编码的蛋白质长度与最初报道的比人类p63长39个氨基酸的小鼠p63相同。通过突变分析，我们发现DLD1和SKOV3细胞在p63的假定DNA结合域中存在杂合突变或多态性。在这些细胞系中，p63是双等位基因表达的。我们得出结论，p63基因的突变在人类细胞系中很少见。DLD1细胞的p63和p53基因均异常这一事实表明，它们可能不参与同一条肿瘤抑制途径。
