Earlier onset of melanotroph carcinogenesis in mice with inherited mutant paternal allele of the retinoblastoma gene

Alexander Yu Nikitin, Daniel J. Riley, Wen Hwa Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4274-4278
Number of pages5
JournalCancer Research
Volume57
Issue number19
StatePublished - Oct 1 1997

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Melanotrophs
Retinoblastoma Genes
Retinoblastoma
Carcinogenesis
Alleles
Genomic Imprinting
Neoplasms
Retinoblastoma Protein
Transgenes
Cell Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Earlier onset of melanotroph carcinogenesis in mice with inherited mutant paternal allele of the retinoblastoma gene. / Nikitin, Alexander Yu; Riley, Daniel J.; Lee, Wen Hwa.

In: Cancer Research, Vol. 57, No. 19, 01.10.1997, p. 4274-4278.

Research output: Contribution to journalArticle

Nikitin, Alexander Yu ; Riley, Daniel J. ; Lee, Wen Hwa. / Earlier onset of melanotroph carcinogenesis in mice with inherited mutant paternal allele of the retinoblastoma gene. In: Cancer Research. 1997 ; Vol. 57, No. 19. pp. 4274-4278.
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