[The retinoblastoma gene: from its basic understanding as a signal mediator for growth and differentiation to its use in the treatment of cancer]

Abstract

The retinoblastoma gene (RB) plays important roles in the genesis of human cancers. Several pieces of evidence have shown that the retinoblastoma protein (Rb) has dual roles in gating cell cycle progression and promoting cellular differentiation. The molecular mechanisms involved in these roles have been elucidated in some biological systems: Rb sequesters the transcription factors of E2F-1 to regulate entry of cell cycle, but enhances the activities of transcription factors such as C/ EBPs to initiate terminal differentiation. Thus, the Rb protein can serve as a mediator of extracellular signals for growth or differentiation. RB also has a tumor suppression function. Introduction of wild-type RB into human tumor cells deficient for RB suppresses their tumorigenicity in nude mice. Similarly, mice with RB+/- genotypes created by gene knockout methods spontaneously develop melanotrophic tumors with complete penetrance. Immune-competent RB+/- mice benefited significantly from adenovirus-mediated RB gene therapy. The fundamental knowledge of Rb function will allow us to take the next steps toward the use of tumor suppressor genes in the treatment of human cancer.