BACKGROUND & AIMS: The KILLER/death receptor (DR)5 has been identified as a potent inducer of apoptosis, and mapped to chromosome 8p21-22, showing frequent allelic loss in gastric cancer. The p53-induced apoptosis is an important biological process to prevent the development of cancer, and is mediated in part by expression of KILLER/DR5 only in cells with wild-type p53 protein, but not in those lacking p53 function. The aim of this study was to determine whether genetic alterations of KILLER/DR5 could be involved in the tumorigenesis of gastric cancer. METHODS: We analyzed the genetic alterations 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 remaining allele. Interestingly, all the mutants inhibit apoptotic cell death in transfection 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 by mutations of KILLER/DR5 may be one of the possible escaping mechanisms against KILLER/DR5-mediated apoptosis and that inactivating mutation of KILLER/DR5 may contribute to the development or progression of a subset of gastric cancers.
BACKGROUND & AIMS: The KILLER/death receptor (DR)5 has been identified as a potent inducer of apoptosis, and mapped to chromosome 8p21-22, showing frequent allelic loss in gastric cancer. The p53-induced apoptosis is an important biological process to prevent the development of cancer, and is mediated in part by expression of KILLER/DR5 only in cells with wild-type p53 protein, but not in those lacking p53 function. The aim of this study was to determine whether genetic alterations of KILLER/DR5 could be involved in the tumorigenesis of gastric cancer. METHODS: We analyzed the genetic alterations 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 remaining allele. Interestingly, all the mutants inhibit apoptotic cell death in transfection 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 by mutations of KILLER/DR5 may be one of the possible escaping mechanisms against KILLER/DR5-mediated apoptosis and that inactivating mutation of KILLER/DR5 may contribute to the development or progression of a subset of gastric cancers.
Authors: Daniel Vallböhmer; Paul Marjoram; Hidekazu Kuramochi; Daisuke Shimizu; Hsuan Jung; Steve R DeMeester; Daniel Oh; Parakrama T Chandrasoma; Kathleen D Danenberg; Tom R DeMeester; Peter V Danenberg; Jeffrey H Peters Journal: J Gastrointest Surg Date: 2007-09 Impact factor: 3.452
Authors: Johannes Lemke; Andreas Noack; Dieter Adam; Vladimir Tchikov; Uwe Bertsch; Christian Röder; Stefan Schütze; Harald Wajant; Holger Kalthoff; Anna Trauzold Journal: J Mol Med (Berl) Date: 2010-03-31 Impact factor: 4.599
Authors: Thomas S Griffith; Brittany Stokes; Tamara A Kucaba; James K Earel; Rebecca L VanOosten; Erik L Brincks; Lyse A Norian Journal: Curr Gene Ther Date: 2009-02 Impact factor: 4.391
Authors: Ji-Youn Han; Eun Kyung Hong; Byung Gil Choi; Jin No Park; Ki Won Kim; Jin Hyung Kang; Jong-Youl Jin; Suk Young Park; Young Seon Hong; Kyung Shik Lee Journal: Med Oncol Date: 2003 Impact factor: 3.064