gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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TRAIL-beta and TRAIL-gamma: first clues for their role in tumor biology of gastric carcinomas

Meeting Abstract

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  • corresponding author presenting/speaker Andreas Krieg - Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Düsseldorf, Deutschland
  • Nadine Göbel - Institut für Pathologie, Universitätsklinikum Düsseldorf
  • Thomas Krieg - Institut für Pathologie, Universitätsklinikum Düsseldorf
  • Jan Schulte am Esch 2nd - Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Düsseldorf
  • Matthias Peiper - Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Düsseldorf
  • Uwe Ramp - Institut für Pathologie, Universitätsklinikum Düsseldorf
  • Wolfram Trudo Knoefel - Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Düsseldorf
  • Helmut Erich Gabbert - Institut für Pathologie, Universitätsklinikum Düsseldorf
  • Csaba Mahotka - Institut für Pathologie, Universitätsklinikum Düsseldorf

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO500

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk610.shtml

Published: March 20, 2006

© 2006 Krieg et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Aims: TRAIL/APO2L (tumor necrosis factor related apoptosis inducing ligand) is a type II transmembrane protein that belongs to the TNF family. TRAIL induces apoptosis in several cancer cells, but not in most normal cells. Here we report on the differential expression of TRAIL variants in gastric carcinomas and determine their apoptotic potential by ectopic expression.

Methods: Transfection assays, Western blot analysis, quantitative real-time PCR, MTT assays, determination of specific apoptotic cell death.

Results: 1. Expression of all TRAIL-isoforms was detectable on mRNA level in all gastric carcinomas and corresponding normal tissues (n = 41). 2. Comparing the expression levels of all TRAIL-variants in normal gastric tissue a statistical significance could only observed between TRAIL-alpha and TRAIL-beta (p = 0.017). In contrast, the differences of expression levels between all TRAIL variants in gastric carcinomas were statistically significant (p < 0.001, p < 0.001, p < 0.001). 3. TRAIL-beta expression were significantly decreased in gastric carcinomas (p < 0.001) leading to a relative increase of the proapoptotic variant TRAIL-alpha. 4. As revealed by transfection assays, a decrease in apoptotic potential was observed for GFP-TRAIL-beta and -gamma, which also became evident from an increase of surviving cells in MTT assays. 5. Immunodetection of the caspase-3/7-dependent death substrate Poly-(ADP-Ribose)-Polymerase (PARP) showed enhancend cleavage only after ectopic expression of GFP-TRAIL-alpha.

Conclusion: The different apoptotic behaviour of the two novel TRAIL splice variants and the significant decrease in the expression of TRAIL-beta on mRNA level in gastric carcinomas provides first evidence for a role of TRAIL-beta in the tumor biology of gastric cancer.