INHIBITION OF TUMOR-CELL PROLIFERATION IN-VITRO AND IN-VIVO BY EXOGENOUS P110(RB), THE RETINOBLASTOMA TUMOR-SUPPRESSOR PROTEIN

Reconstitution of retinoblastoma gene (RE) deficient tumor cells with RE generally leads to growth suppression in vitro and/or reduced tumor igenicity in nude mice. An alternate approach to gene replacement is t he delivery of the RE gene product (p110(RB)) into cells lacking its e xpression. In this report we demonstrate that exogenously added p110(R B) is taken up by and localized to the nucleus of cultured cells and h as growth suppression properties similar to endogenous RE. RE-negative (RB(neg)) tumor cells are preferentially growth inhibited while most RE-positive (RB(pos)) tumor cells and normal cells are much less sensi tive. We have extended these studies to relevant nude mouse xenograft models for human lung cancer. Local or systemic administration of p110 (RB) inhibits armor growth in treated animals. These results represent the first use of a tumor suppressor protein as a potential cancer the rapeutic.