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Molecular and cellular biology
Dec, 2004;24 (23): 10406-15.

Genetic interaction between Rb and K-ras in the control of differentiation and tumor suppression.

Chiaki Takahashi, Bernardo Contreras, Roderick T Bronson, Massimo Loda, Mark E Ewen
Author Information
  1. Chiaki Takahashi: Department of Medial Oncology, Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, USA.
PMID: 15542848 DOI: 10.1128/MCB.24.23.10406-10415.2004

Abstract

Although the retinoblastoma protein (pRb) has been implicated in the processes of cellular differentiation, there is no compelling genetic or in vivo evidence that such activities contribute to pRb-mediated tumor suppression. Motivated by cell culture studies suggesting that Ras is a downstream effector of pRb in the control of differentiation, we have examined the tumor and developmental phenotypes of Rb and K-ras double-knockout mice. We find that heterozygosity for K-ras (i) rescued a unique subset of developmental defects that characterize Rb-deficient embryos by affecting differentiation but not proliferation and (ii) significantly enhanced the degree of differentiation of pituitary adenocarcinomas arising in Rb heterozygotes, leading to their prolonged survival. These observations suggest that Rb and K-ras function together in vivo, in the contexts of both embryonic and tumor development, and that the ability to affect differentiation is a major facet of the tumor suppressor function of pRb.

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Grants

  1. P01 CA089021/NCI NIH HHS
  2. R01 CA065842/NCI NIH HHS
  3. P01CA89021/NCI NIH HHS
  4. R01CA65842/NCI NIH HHS

MeSH Term

Alleles
Animals
Bromodeoxyuridine
Cell Cycle
Cell Differentiation
Cell Proliferation
Cells, Cultured
Coloring Agents
Crosses, Genetic
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Genes, ras
Genotype
Heterozygote
Immunohistochemistry
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Muscle, Skeletal
Mutation
MyoD Protein
Neoplasms
Pituitary Gland
Polymerase Chain Reaction
Protein Binding
Retinoblastoma Protein
Ribonucleases
Time Factors
Transcriptional Activation
Transgenes

Chemicals

Coloring Agents
MyoD Protein
Retinoblastoma Protein
Ribonucleases
Bromodeoxyuridine
Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Word Cloud

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