First Author | Yang H | Year | 2002 |
Journal | Mol Cell Biol | Volume | 22 |
Issue | 9 | Pages | 3103-10 |
PubMed ID | 11940667 | Mgi Jnum | J:75738 |
Mgi Id | MGI:2177713 | Doi | 10.1128/MCB.22.9.3103-3110.2002 |
Citation | Yang H, et al. (2002) Tumor suppression by a severely truncated species of retinoblastoma protein. Mol Cell Biol 22(9):3103-10 |
abstractText | 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. |