Knockout mouse models and mammary tumorigenesis.
The generation of transgenic mice overexpressing activated forms of oncogenes has greatly advanced our understanding into their roles in mammary tumor initiation, promotion and progression. However, targeted disruption of tumor suppressor genes often results in lethality at stages prior to mammary tumor formation. This obstacle can now be overcome using several approaches including conditional knockouts that delete genes of interest in a spatial and temporal manner. This review summarizes recent studies on tumor suppressor genes, including APC, ATM, BRCA1, BRCA2, PTEN and p53, in knockout mouse models and our understanding of the possible mechanisms underlying mammary tumorigenesis.
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Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10/9N105, Bethesda, MD 20892, USA. chuxiad@bdg10.niddk.nih.gov
Brodie
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D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019398:Genes, BRCA1; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D025601:Adenomatous Polyposis Coli Protein; D024682:BRCA2 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human