Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 89
Overexpression of Lifeguard (LFG) suppresses TRAIL-induced apoptosis and activates
NF-kB
Kerstin Reimers, Claudia YU Choi, Susanne Kall, Peter M Vogt
Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover,
Podbielskistr. 380, 30659 Hannover, Germany, E-mail: Reimers.Kerstin@MH-
Hannover.de
TRAIL is a promising cytokine for cancer therapies, which preferentially induces apoptosis in
cancer cells by binding to death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. Other tumor
cells, however, are resistant against TRAIL and require aditional treatment with radio- or
chemotherapy. Lifeguard (LFG) is an anti-apoptotic protein related to the Bax-inhibitory
protein 1 (BI-1). Cells expressing LFG are resistant against TRAIL- and Fas-induced cell
death. We were able to show that this protective effect can be transmitted to non-LFGexpressing
Fas-sensitive cell lines using transient transfection of LFG. In order to characterize
the functional mechanism of this antiapoptotic protein we determined the DNA-binding
activity of the NF-kB p65 subunit in cells overexpressing LFG. The cells showed an increased
nuclear translocation of the p65 subunit. The resulting activation of NF-kB depends on IkBa
degradation. An increased NF-kB activity is correlated with a sensitization of the treated cells
against induction of apoptosis by TRAIL. Many cancer cells show constitutive activation of
NF-kB leading to insensitiviy against therapeutically induced apoptosis. High expression of
LFG might contribute to cell death prevention by activation of NF-kB.
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