Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 19
Downregulation of Lifeguard leads to sensitization against TRAIL induced apoptosis in
tumor cell lines
Claudia YU Choi, Kerstin Reimers, Susanne Kall, Peter M. Vogt
Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover,
Podbielskistr. 380, 30659 Hannover, Germany, E-mail: Choi.Claudia@MH-
Hannover.de
A dysbalance between apoptosis and proliferation plays an essential role in tumor
development. The expression of anti-apoptotic proteins promotes tumorigenesis and
resistance to chemotherapy. TRAIL is the most promising candidate for tumor selective death
receptor-activation. It activates the death receptors TRAIL-1 and TRAIL 2 inducing apoptosis
preferentially in tumor cells but not in normal tissue. Specific means to sensitize tumor cells
for TRAIL are desirable. Lifeguard (LFG) is a protein with inhibitory function on Fasmediated
apoptosis. We hypothesized that LFG inhibits TRAIL-induced apoptosis. We
determined high LFG-expression-levels in A549 cells and comparing tumor cell lines of
different origins we found that TRAIL-sensitivity correlated with high LFG-expressionlevels.
To selectively interfere with expression of LFG, an antisense construct with effective
down-regulation was introduced to A549 cells.After treatment, the sensitivity to TRAIL was
enhanced with up-regulation of the apoptotic activity. In conclusion, LFG is expressed in
many TRAIL-resistant tumor cell lines and the inhibition of LFG-expression was sufficient to
sensitize A549 cells from TRAIL-mediated apoptosis. Our findings indicate that LFG is a
protein with pathogenic function in tumorigenesis with new therapeutic options in cancer
therapy targeting LFG.
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