title: Induction of apoptosis in Mv1Lu cells by expression of competitive RB1 mutants.
abstract: The Retinoblastoma tumor suppressor gene (RB1) plays a role in a variety of human cancers. Experimental analyses have indicated that the protein product of the RB1 gene (pRb) plays a role in cell cycle regulation. pRb function is dependent on its ability to bind to cellular factors, which is facilitated by multiple protein binding domains within pRb. Mutations within these domains which eliminate the ability of pRb to bind its targets result in loss of function. Although loss of pRb function may lead to uncontrolled cellular proliferation, tumorigenesis is not the only response to pRb inactivation. Examination of various tissues from RB1-nullizygous mouse embryos showed problems in differentiation and induction of apoptosis, suggesting that the ultimate response to the loss of pRb is influenced by cellular context. It has previously been demonstrated in RB1-negative Saos-2 cells that co-expression of the C-terminal domain of pRb with wildtype pRb resulted in escape from G1 arrest and continued cell cycling. In this paper we demonstrate that in RB1-positive Mv1Lu cells, expression of the A/B pocket region or the N-terminus (when combined with a nuclear localization signal), but not the C-terminal domain, is able to competitively disrupt the function of the endogenous pRb, and that the result of this disruption is apoptosis.
authors.affiliation: Department of Molecular Genetics, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Whitaker
authors.forename: M F
authors.initials: MF
authors.lastname: Hansen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001667:Binding, Competitive; D002460:Cell Line; D004847:Epithelial Cells; D015972:Gene Expression Regulation, Neoplastic; D016161:Genes, Retinoblastoma; D008168:Lung; D008907:Mink; D016254:Mutagenesis, Insertional; D010641:Phenotype; D016160:Retinoblastoma Protein / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
chemical_list: D016160:Retinoblastoma Protein