Protein expression of the RB-related gene family and SV40 large T antigen in mesothelioma and lung cancer

Mutational inactivation of the RE-related gene RBL2/ p130 has been reported as a common and important prognostic factor in human lung cancer. To exami ne the role of the RE-related gene family in lung cancer we analysed the pr otein expression of the RE gene in cell Lines obtained from 83 patients wit h small cell lung cancer (SCLC) and 114 patients with non-SCLC that include d 21 novel lung tumor samples. While we detected five new SCLC with mutant RE expression (RB inactivation in 75/83; 90.4%), we did not detect any RE m utations in the new non-SCLC cell lines (RB inactivation in 13/114 non-SCLC and mesothelioma; 11.4%), In addition, we detected expression of a full-le ngth RBL1/p107 and RBL2/p130 species in every sample tested (RBL1 or RBL2 i nactivation in 0/69) and confirmed that both RE-related gene products retai n functional binding activity to the E1A viral oncoprotein. Since expressio n of SV40 Large T antigen (Tag) has been reported in a subset of human lung tumors where it may inactivate RBL1 and RBL2, we also examined mesotheliom a and non-mesothelioma lung tumors for Tag expression. Although we detected a faint 85 kDa protein species using specific anti-Tag antibodies, this si gnal migrated slightly faster than Tag extracted from Cos7 cells and did no t exhibit binding activity to the RE or RBL1 proteins, Finally, we subjecte d 11 lung cancer cell lines to nucleotide sequencing and did not detect mut ations within the C-terminal RBL2 exons 19-22 as recently reported. While t he RB/p16 tumor suppressor pathway is targeted for mutations in 100% of lun g cancers, mutational inactivation of the related RBL1 and RBL2 genes is a rare event.