Tumor suppression by a severely truncated species of retinoblastoma protein.

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Chimera, Gene-Deletion, Gene-Expression-Regulation-Neoplastic, Human, Lens-Crystalline, Mice, Mice-Knockout, Mice-Transgenic, Pituitary-Neoplasms, RNA-Messenger, Retinoblastoma-Protein, Stem-Cells, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Survival-Rate, Transgenes

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Mol Cell Biol 2002 May; 22(9): 3103-10


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.