Tumor suppression by a severely truncated species of retinoblastoma protein.
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.
Yang
Hong
H
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Williams
Bart O
BO
Hinds
Phillip W
PW
Shih
T Shane
TS
Jacks
Tyler
T
Bronson
Roderick T
RT
Livingston
David M
DM
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
D012333:RNA, Messenger; D016160:Retinoblastoma Protein