gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Expression profile of TRAIL and DR5 splice variants in human renal cell carcinoma

Meeting Abstract

  • corresponding author presenting/speaker Nadine Göbel - Universitätsklinikum, Düsseldorf, Deutschland
  • Andreas Krieg - Universitätsklinikum, Düsseldorf
  • Uwe Ramp - Universitätsklinikum, Düsseldorf
  • Nils Wethkamp - Universitätsklinikum, Düsseldorf
  • Tobias Kempf - Universitätsklinikum, Düsseldorf
  • Helmut E. Gabbert - Universitätsklinikum, Düsseldorf
  • Csaba Mahotka - Universitätsklinikum, Düsseldorf

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP489

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dkk2006/06dkk599.shtml

Published: March 20, 2006

© 2006 Göbel et al.
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Outline

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Objective: Tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L) is a member of the TNF family that induces programmed cell death in a variety of neoplastic cell types, but only in a few non-neoplastic cells. In this study, we report on the tumor progression dependent expression of two novel alternative splice variants of TRAIL – identified by our group – in neoplastic and non-neoplastic human cells lacking either exon 3 (TRAIL-b) or exons 2 and 3 (TRAIL-g). Moreover, we analyzed the expression of the TRAIL receptor DR5 (TRICK2) and its alternative splice variants TRICK2a and TRICK2b during tumor progression of renal cell carcinoma (RCC).

Methods: Determination of tumour grading and staging by histopathological examination, total RNA-isolation, RT-PCR, statistical analysis by the Mann-Whitney and Wilcoxon test.

Results:1. TRAIL-a,-b and -g are significantly (p=0.029, 0.024, 0.008) higher expressed in non-neoplastic than in neoplastic cells.2. The expression ratio of TRAIL-β and –g shows a significant (p=0.002) difference in normal vs. tumor cells.3. TRAIL-a,-b and -g were not regulated during tumor progression from pT1/2 to advanced pT3 stage.4. The expression levels of the DR5 receptor variants TRICK2a and TRICK2b were not affected in normal vs. tumor cells. Interestingly, the expression levels of TRICK2a significantly (p= 0.012) increased in tumor stage pT1/2 vs. non-neoplastic cells.5. The expression of TRICK2b in pT1/2 stages significantly (p=0.037) decreased in advanced tumor stages (pT3).

Conclusions: Our data suggest that all three TRAIL variants - mainly TRAIL-g - and TRICK2b are significantly decreased in tumor cells, indicating their potential role in RCCs. Alternative splicing of the immature TRAIL-RNA as well as the TRICK2-RNA might be involved in fine tuning of TRAIL-induced apoptosis and underlines the complexity of the TRAIL-system in renal cell carcinoma.