Abstract
Overcoming apoptosis resistance to chemotherapy and radiation may lead to a reduction in gastric cancer death. We hypothesize that the apoptotic machinery in gastric cancer cells is dependent upon specific cellular conditions. In the course of our study of the expression of apoptosis-related genes in human gastric cancer cell lines, we have identified a cDNA clone which predicts an alternative form of caspase-9. The caspase-9 variant, which we designated as caspase-9 beta, retained a truncated structure of native caspase-9 without its catalytic domain and was expressed in seven cell lines from human gastric cancer. Among the cell lines examined, MKN-28 cells, which exhibited the most resistance against apoptotic stimuli, expressed the highest level of caspase-9 beta. The induction of apoptosis by staurosporine or actinomycin D was markedly suppressed in caspase-9 beta-transfected HeLa cells. These results are consistent with our hypothesis that the caspase-9 beta may be an endogenous dominant-negative molecule which attenuates apoptotic activity in human gastric cancer cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Schechter NR, Portlock CS, Yahalom J. Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone. J Clin Oncol 1998; 16: 1916–1921.
Hanazaki K, Sodeyama H, Yokoyama S, et al. Postoperative chemotherapy may improve prognosis in unresectable gastric cancer. J Clin Gastroenterol 1998; 26: 269–273.
Keller SM, Ryan LM, Coia LA, et al. High dose chemoradiotherapy followed by esophagectomy for adenocarcinoma of the esophagus and gastroesophageal junction: results of a phase II study of the eastern cooperative oncology group. Cancer 1998; 83: 1908–1916.
Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, et al. The Ced-3/interleukin 1 beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2 alpha are substrates for the apoptotic mediator CPP32. J Biol Chem 1996; 271: 27099–27106.
Thornberry NA, Lazebnik Y. Caspases: enemies within. Science 1998; 281: 1312–1316.
Hu Y, Benedict MA, Wu D, Inohara N, Nunez G. Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation. Proc Natl Acad Sci USA 1998; 95: 4386–4391.
Pan G, O'Rourke K, Dixit VM. Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex. J Biol Chem 1998; 273: 5841–5845.
Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Alnemri ES. Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization. Mol Cell 1998; 1: 949–957.
Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998; 282: 1318–1321.
Hojo H. Establishment of cultured cell lines of human stomach cancer origin and their morphological characteristics. Niigata Igakukai Zasshi 1977; 9: 281–285.
Sekiguchi M, Sakakibara K, Fujii G. Establishment of cultured cell lines derived from a human gastric carcinoma. Jpn J Exp Med 1978; 48: 61–68.
Akiyama S, Amo H, Watanabe T, et al. Characteristics of three human gastric cancer cell lines, NU-GC-2, NU-GC-3 and NU-GC-4. Jpn J Surg 1988; 18: 438–446.
Satoh T, Hoshikawa Y, Satoh Y, Kurata T, Sairenji T. The interaction of mitogen-activated protein kinases to Epstein-Barr virus activation in Akata cells. Virus Genes 1998; 18: 57–64.
Niwa H, Yamamura K-I, Miyazaki J-I. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 1991; 108: 193–200.
Zhang J, Liu X, Scherer DC, van Kaer L, Wang X, Xu M. Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45. Proc Natl Acad Sci USA 1998; 95: 12480–12485.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55–63.
Li P, Nijihawan D, Budihardijo I, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 91: 479–489.
Osaki M, Tatebe A, Goto H, Hayashi M, Oshimura M, Ito H. 5-Fluorouracil (5-FU) induced apoptosis in gastric cancer cell lines: role of the p53 gene. Apoptosis 1997; 2: 221–226.
Hayashi H, Tatebe S, Osaki M, Goto A, Suzuki Y, Ito H. Expression of Fas antigen and its mediation of apoptosis in human gastric cancer cell lines. Jpn J Cancer Res 1997; 88: 49–55.
Seol D-W, Billiar T. A caspase-9 variant missing the catalytic site is an endogenous inhibitor of apoptosis. J Biol Chem 1999; 274: 2072–2076.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Izawa, M., Mori, T., Satoh, T. et al. Identification of an alternative form of caspase-9 in human gastric cancer cell lines: a role of a caspase-9 variant in apoptosis resistance. Apoptosis 4, 321–325 (1999). https://doi.org/10.1023/A:1009639103291
Issue Date:
DOI: https://doi.org/10.1023/A:1009639103291