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Session X : Cell death in cancer Poster X, 67
Functional Analysis of the Anti-Apoptotic Livin Protein
Christina Mensger, Irena Crnkovic-Mertens, Claire Cullmann, Karin Butz and Felix
Hoppe-Seyler
Infection and Cancer, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242,
D-69120 Heidelberg, Germany. E-mail: c.mensger@dkfz.de
Cancer cells are typically characterized by increased resistance to apoptosis, which enables
their survival under abnormal growth stimulation. Moreover, deficiency in apoptosis is
considered to be a major cause for therapeutic resistance of tumours in the clinic, since many
chemo- and radiotherapeutic agents act through the induction of apoptosis. The functional
inhibition of specific anti-apoptotic factors should therefore provide a rational basis for the
development of novel therapeutic strategies.
Livin is a relatively new member of the "Inhibitors of Apoptosis Protein" (IAP) family.
Initially associated with malignant melanoma, it recently has been found that Livin is also
expressed in many additional cancers, such as lung cancer. Notably, livin gene expression is
typically detectable in the tumor cells but not, or to substantially lower levels, in the
corresponding normal tissue.
We found that the targeted inhibition of Livin by RNA interference (RNAi) led to a proapoptotic
sensitization towards different pro-apoptotic stimuli, which was specific for Livinexpressing
tumor cells. Moreover, long-term inhibition of Livin expression in clonogenic
survival assays led to the elimination of Livin-expressing tumor cells, even in the absence of
additional pro-apoptotic stimuli. Isoform-specific RNAi showed that the biological
significance of the two known Livin isoforms, Livin " and Livin #, can strongly differ,
possibly in a cell-dependent manner. Ongoing work concentrates on the elucidation of the
critical intracellular pathways and natural interaction partners which mediate the antiapoptotic
activity of Livin.
Based on its cancer-associated expression pattern, Livin may serve as a novel diagnostic and
prognostic tumor marker. In addition, the targeted inhibition of Livin could represent a new
antitumor strategy.
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