RECONSTITUTION OF THE RB GENE SUPPRESSES THE GROWTH OF SMALL-CELL LUNG-CARCINOMA CELLS CARRYING MULTIPLE GENETIC ALTERATIONS

Multiple genetic alterations, including inactivation of the RB gene, o ccur commonly in small-cell lung carcinoma (SCLC). To assess a functio nal role of RB inactivation in the development of SCLC, an RB expressi on plasmid was introduced by stable transfection into SCLC cell lines, Lu-135 and N417, in which the RB gene was inactivated. Lu-135 and N41 7 cells transfected with the wild-type RB gene formed G418-resistant c olonies twofold less efficiently than those with a mutated RB gene or with the control vector. Intact exogenous wild-type RB genes were dete cted only in approximately 20% of G418-resistant clones; three of 14 i n Lu-135 and three of 16 in N417, respectively. Transcripts from the t ransfected RB gene were also detected in two of these three clones fro m Lu-135 and two of three from N417 but the amount of RB mRNA and prot ein was less than one fifth of that in normal fibroblast celts WI-38. Furthermore, clones with exogenous wild-type RB expression showed eith er reduced growth rates in culture or suppressed tumorigenicity in nud e mice. These findings suggest that functional correction of the RB ge ne is sufficient to suppress the growth of SCLC cells, even though sev eral other genetic alterations in the cells remain uncorrected.