Mouse models in tumor suppression

Oncogene. 1998 Dec 24;17(25):3385-400. doi: 10.1038/sj.onc.1202573.

Abstract

Genetic lesions found in tumors are often targeted to the negative growth regulatory tumor suppressor genes. Much of our understanding of tumor suppressor gene function is derived from experimental manipulations in cultured cells. Recently, however, the generation of mice with germ line tumor suppressor gene mutations through gene targeting in embryonic stem cells has provided another dimension by allowing experimental studies of tumor suppressor function in an organismal context. Novel insights into the role of tumor suppressors in development, differentiation, cell cycle control, and tumor suppression have been obtained from the studies on these 'knockout' mice. In addition, such mice may serve as disease models for humans with inherited cancer predisposition syndromes. Perhaps the greatest advantage of many of the mouse tumor suppressor models is that they facilitate study of the roles of tumor suppressor gene loss in tumor initiation and progression in vivo. Moreover, derivation of primary cells from tumor suppressor-deficient mice has provided an important resource for in vitro studies on the role of targeted genes in cell cycle regulation, DNA damage response, regulation of apoptotic pathways, and preservation of genomic stability. In this review, we discuss some of the mechanistic insights provided by tumor suppressor-deficient mice and their utility as models for human cancer syndromes.

Publication types

  • Review

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / physiology
  • BRCA2 Protein
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / physiology
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Disease Models, Animal*
  • Genes, Tumor Suppressor / genetics*
  • Genes, Tumor Suppressor / physiology
  • Genetic Predisposition to Disease
  • Humans
  • Ligases*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Mice, Knockout / genetics*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology
  • Neoplasms / genetics*
  • Neurofibromin 1
  • Neurofibromin 2
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / physiology
  • Proteins / genetics
  • Proteins / physiology
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / physiology
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein
  • WT1 Proteins

Substances

  • Adenomatous Polyposis Coli Protein
  • BRCA1 Protein
  • BRCA2 Protein
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • Neurofibromin 1
  • Neurofibromin 2
  • Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • Tumor Suppressor Protein p14ARF
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • WT1 Proteins
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Ligases
  • VHL protein, human