RT Journal Article SR Electronic T1 Modulation of Anti-apoptosis by Endogenous IAP Expression in MKN45 Human Gastric Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2713 OP 2717 VO 25 IS 4 A1 KAZUYA ENDO A1 SHUNJI KOHNOE A1 EIJI TSUJITA A1 AKIHIRO WATANABE A1 HIDEAKI NAKASHIMA A1 HIDEO BABA A1 YOSHIHIKO MAEHARA YR 2005 UL http://ar.iiarjournals.org/content/25/4/2713.abstract AB Background: This study was designed to clarify differences in apoptotic signal transduction between gastric cancer cells and leukemia cells. Materials and Methods: In order to study apoptotic signal transduction of gastric cancer cells, MKN45 gastric cancer cells expressing the wild-type p53 gene and U937 myeloid leukemia cells expressing a mutated p53 gene were prepared. Cisplatin (CDDP) was used to induce apoptosis. We compared apoptotic signal transduction downstream to mitochondria between those two lines. Results: In contrast to U937 cells, MKN45 gastric cancer cells revealed delayed response in release of mitochondrial cytochrome c into the cytosol following caspase 3 activation. In signal pathways downstream of caspase 3 cleavage, of the three substrates detected, poly (ADP-ribose) polymerase (PARP) and PKC (protein kinase c) %thou were not activated in MKN45 cells compared with U937 cells, resulting in delayed appearance of DNA ladder formation during CDDP-induced apoptosis. MKN45 constitutively expressed cIAP1, regardless of CDDP treatment, compared with no expression in U937. Drug sensitivity testing showed that MKN45 was more resistant to CDDP than U937 cells. Conclusion: We demonstrated that there is a delayed mitochondrial response and incomplete activation of caspase 3 in MKN45 gastric cancer cells compared with U937 leukemia cells. In addition, there was endogenous cIAP1 expression in MKN45 cells, which may be a factor in the presumed anti-apoptotic system in these human gastric cancer cells. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved