| Autor: |
Torre, Gabriella Della, Pasquini, Graziella, Pilotti, Silvana, Alasio, Loredana, Civelli, Enrico, Cozzi, Guido, Milella, Marco, Salvetti, Monica, Pierotti, Marco A., Severini, Aldo |
| Zdroj: |
Diagnostic Molecular Pathology; March 2000, Vol. 9 Issue: 1 p41-46, 6p |
| Abstrakt: |
Tumor suppressor protein p53 is a positive regulator of MDM2gene expression and the mdm2 protein can bind to p53, preventing the transactivation of p53 responsive genes, thus mimicking TP53mutation. The authors looked for alterations that could affect, directly and indirectly, p53 function in 13 patients with extrahepatic cholangiocarcinoma. Molecular analysis by single strand conformation polymorphism and DNA sequencing revealed that TP53gene mutations occurred in only 2 of 13 cholangiocarcinomas. High levels of mdm2 protein were found, by immunohistochemical staining, in 61 of the cholangiocarcinomas and in almost all specimens (70) displaying stabilized p53 protein in the absence and in the presence of TP53mutations. The finding of co-overexpressed mdm2 and p53 proteins in cholangiocarcinomas indicates that they can upregulate the expression of mdm2 protein to a level sufficient for binding and accumulating p53 in a presumably inactive complexed form. The presence of TP53mutations or upregulation of MDM2gene expression in 9 of the 13 cholangiocarcinomas strongly supports that the impairment of the p53 pathway is an important and specific step in cholangiocarcinoma pathogenesis. At variance with other authors, no alteration of p16ink4/ CDKN2gene was observed in all 13 cholangiocarcinomas. |
| Databáze: |
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