Inactivating mutations of KILLER/DR5 gene in gastric cancers

Citation
Ws. Park et al., Inactivating mutations of KILLER/DR5 gene in gastric cancers, GASTROENTY, 121(5), 2001, pp. 1219-1225
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
GASTROENTEROLOGY
ISSN journal
0016-5085 → ACNP
Volume
121
Issue
5
Year of publication
2001
Pages
1219 - 1225
Database
ISI
SICI code
0016-5085(200111)121:5<1219:IMOKGI>2.0.ZU;2-7
Abstract
Background & Aims: The KILLER/death receptor (DR)5 has been identified as a potent inducer of apoptosis, and mapped to chromosome 8p21-22, showing fre quent allelic loss in gastric cancer. The p53-induced apoptosis is an impor tant biological process to prevent the development of cancer, and is mediat ed in part by expression of KILLER/DR5 only in cells with wild-type p53 pro tein, but not in those lacking p53 function. The aim of this study was to d etermine whether genetic alterations of KILLER/DR5 could be involved in the tumorigenesis of gastric cancer. Methods: We analyzed the genetic alterati ons of KILLER/DR5 and p53 in 43 gastric cancers and the loss of function of KILLER/DR5 mutants, detected in this study. Results: We found 3 KILLER/DR5 missense mutations (7%), and 2 of them showed allelic loss in the remainin g allele. Interestingly, all the mutants inhibit apoptotic cell death in tr ansfection studies. We also found 6 p53 mutations (14%). Interestingly, the tumors containing the KILLER/DR5 mutation did not carry the p53 mutation. Conclusions: These results suggest that inactivation of KILLER/DR5 caused b y mutations of KILLER/DR5 may be one of the possible escaping mechanisms ag ainst KILLER/DR5-mediated apoptosis and that inactivating mutation of KILLE R/DR5 may contribute to the development or progression of a subset of gastr ic cancers.