Mutational analysis of proapoptotic ARTS P-loop domain in common human cancers.

Mounting evidence indicates that deregulation of apoptosis is involved in mechanisms of cancer development. ARTS is released from mitochondria into the cytosol during apoptosis, promoting caspase activation by neutralizing the inhibition of inhibitor of apoptotic protein (IAP) on caspases. ARTS contains a P-loop GTP-binding domain, which is essential for the apoptotic function of ARTS. The aim of this study was to ascertain whether a genetic alteration of ARTS gene is involved in the development of human cancers possibly by inactivating the apoptotic function of ART. We analyzed the coding region of the P-loop domain of human ARTS gene for the detection of somatic mutations in 100 gastric carcinomas, 100 non-small cell lung cancers, and 69 hepatocellular carcinomas using a polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP). However, there was no mutation in the P-loop coding region in the cancers. The data presented here suggest that ARTS P-loop is not frequently mutated in gastric, lung, and hepatocellular carcinomas, and that apoptosis deregulation in cancers is not dependent on the mutation of ARTS gene.