[The retinoblastoma gene: from its basic understanding as a signal mediator for growth and differentiation to its use in the treatment of cancer].
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.
Lee
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Dept. of Molecular Medicine/Institute of Bio-technology, University of Texas Health Science Center, USA.
Lee
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D000818:Animals; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy; D016160:Retinoblastoma Protein / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors