title: Earlier onset of melanotroph carcinogenesis in mice with inherited mutant paternal allele of the retinoblastoma gene.
abstract: The role of genomic imprinting in the development of tumors with defective retinoblastoma protein function remains debatable. Disruption of either parental allele of the murine retinoblastoma (Rb) gene is sufficient for spontaneous melanotroph carcinogenesis to occur in almost all Rb+/- mice. Nevertheless, mice with a disrupted paternal Rb allele succumb to tumors faster. In these animals, the first foci of proliferating atypical Rb-negative cells appear and progress to overtly malignant tumors earlier. In addition, more foci of early atypical proliferation are observed. In Rb+/- mice, however, parental origin influences neither Rb expression nor proliferation of melanotrophs. Accordingly, Rb-/- mice rescued by the human RB transgene transmitted either paternally or maternally have similar survival rates. Taken together, the data point to the existence of an imprinted gene in an Rb-linked locus. The function of this gene affects the onset of melanotroph carcinogenesis, likely by controlling preferential survival of the cells with secondary loss of the Rb maternal allele. Rb+/- mice may serve as useful models to identify and characterize genomic imprinting mechanisms influencing carcinogenesis associated with Rb loss of function.
authors.affiliation: Department of Molecular Medicine, Institute of Biotechnology, The University of Texas Health Science Center, San Antonio 78245-3207, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Nikitin
authors.forename: D J
authors.initials: DJ
authors.lastname: Riley
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D017668:Age of Onset; D000483:Alleles; D000818:Animals; D002455:Cell Division; D005260:Female; D016161:Genes, Retinoblastoma; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction