Mouse models in tumor suppression

Genetic lesions found in tumors are often targeted to the negative growth r egulatory tumor suppressor genes. Much of our understanding of tumor suppre ssor gene function is derived from experimental manipulations in cultured c ells. Recently, however, the generation of mice with germ line tumor suppre ssor gene mutations through gene targeting in embryonic stem cells has prov ided another dimension by allowing experimental studies of tumor suppressor function in an organismal context. Novel insights into the role of tumor s uppressors in development, differentiation, cell cycle control, and tumor s uppression 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 role s of tumor suppressor gene loss in tumor initiation and progression in vivo . Moreover, derivation of primary cells from tumor suppressor-deficient mic e has provided an important resource for in vitro studies on the role of ta rgeted genes in cell cycle regulation, DNA damage response, regulation of a poptotic pathways, and preservation of genomic stability. In this review, w e discuss some of the mechanistic insights provided by tumor suppressor-def icient mice and their utility as models for human cancer syndromes.