Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 32
Alternative splicing of TRAIL and DR5: first clues for their role in human renal cell
carcinoma
N Göbel, A Krieg, U Ramp, N Wethkamp, T Kempf, HE Gabbert, C Mahotka
Institute of Pathology, Heinrich Heine-University, Moorenstr.5, 40225 Düsseldorf,
Germany, nadine@wcv-mail.de
Objective: Tumor necrosis factor (TNF) related apoptosis-inducing ligand (TRAIL/APO2L)
induces programmed cell death in a variety of neoplastic cell types, but only in a few nonneoplastic
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-beta) or exons 2 and 3 (TRAILgamma).
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-alpha, -beta and -gamma are
significantly (p=0.029, 0.024, 0.008) higher expressed in non-neoplastic than in neoplastic
cells. 2. The expression ratio of TRAIL-beta and –gamma shows a significant (p=0.002)
difference in normal vs. tumor cells. 3. All TRAIL variants 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-gamma - 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.
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