title: Tumor suppression by a severely truncated species of retinoblastoma protein.
abstract: Rb(+/+):Rb(-/-) chimeric mice are healthy until early in adulthood when they develop lethal pituitary tumors composed solely of Rb(-/-) cells. In an effort to delineate the minimal structures of the retinoblastoma protein necessary for RB tumor suppression function, chimeric animals derived from stably transfected RB(-/-) embryonic stem (ES) cells were generated. One such ES cell transfectant expressed a human RB allele encoding a stable, truncated nuclear derivative lacking residues 1 to 378 (Delta 1-378). Others encoded either wild-type human RB or an internally deleted derivative of the Delta 1-378 mutant. All gave rise to viable chimeric animals with comparable degrees of chimerism. However, unlike control mice derived, in part, from naive Rb(-/-) ES cells or from ES cells transformed by the double RB mutant, Delta 1-378/Delta exon22, animals derived from either wild-type RB- or Delta 1-378 RB-producing ES cells failed to develop pituitary tumors. Thus, in this setting, a substantial fraction of the RB sequence is unnecessary for RB-mediated tumor suppression.
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
authors.forename: Phillip W
authors.initials: PW
authors.lastname: Hinds
authors.forename: T Shane
authors.initials: TS
authors.lastname: Shih
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: David M
authors.initials: DM
authors.lastname: Livingston
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics / Q000473:pathology; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007908:Lens, Crystalline / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D015996:Survival Rate; D019076:Transgenes / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D016160:Retinoblastoma Protein