Genetic instability in animal tumorigenesis models.
In this review I have attempted to a describe some of the recent mouse tumour models and their impact on our understanding of cancer aetiology. The focus has been on cell cycle regulatory genes and DNA repair genes which are likely to affect cancer development at least in part through genetic instability mechanisms. The cell cycle regulatory genes classified as tumour suppressors, TP53 and RB, maintain genomic stability and inhibit cancer through their roles in preserving cell cycle checkpoints. The cell cycle inhibitors have variable effects on cancer prevention, and their role in preserving genetic stability remains largely unexplored. The DNA repair gene models described here show the most direct connection between genetic instability and cancer, even in the absence of demonstrable cell cycle effects. It should be clear that the development of mice deficient in cell cycle control or DNA repair will provide useful tools for studying the interplay of these processes with genetic instability and cancer. Important new insights into the mechanisms of cancer initiation and progression are likely to come increasingly from such models in the coming years.
Donehower
L A
LA
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D016213:Cyclins / Q000235:genetics / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004195:Disease Models, Animal; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D051379:Mice; D016296:Mutagenesis / Q000235:genetics* / Q000502:physiology; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000502:physiology
D016213:Cyclins; D019098:Telomerase