gms | German Medical Science

Aims: The X-linked inhibitor of apoptosis (XIAP) is one of the most potent caspase inhibitors of the inhibitor of apoptosis (IAP)-family members. Only recently, an antagonist of XIAP has been identified, named Smac/DIABLO. Since a dysbalance of pro- and antiapoptotic regulators are thought to play a major role in tumor progression, the aim of the present study was to explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs).

Methods: XIAP and Smac/DIABLO mRNA and protein expression was analysed in primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA.

Results: 1. XIAP and Smac/DIABLO mRNA expression was found in all RCCs. 2. The relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages (p=0.0002) and also with tumour dedifferentiation (p=0.04). 3. Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. 4. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. 5. The mRNA expression ratio between XIAP and Smac/DIABLO markedly increased during progression from early (pT1) to advanced (pT3) tumour stages.

Conclusions:.The delicate balance between antiapoptotic XIAP and proapoptotic Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of XIAP over Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.