p53-Dependent Apoptosis In Vivo: Impact of p53 Inactivation on Tumorigenesis
- *Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599; †Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; ‡Howard Hughes Medical Institute and §Department of Pediatrics, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15213
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Excerpt
Loss of tumor suppressor function clearly contributes to the multistep process of tumorigenesis, as evidenced by the frequent mutation of these genes in human cancer (Marshall 1991; Hinds and Weinberg 1994). Investigation into the mechanisms by which inactivation of tumor suppressors contributes to tumorigenesis is therefore central to understanding cancer. The p53 gene is presently the most frequently mutated tumor suppressor gene in human cancers. Moreover, tumors of many different cell types harbor p53 mutations. Exactly how the disruption of p53 contributes to the genesis of these tumors and whether the contribution is the same or different in cancers of different cell types is not understood.
On the basis of recent in vitro studies of p53 function, at least two models can be proposed (Fig. 1). In cultured fibroblasts, p53 appears to have a role in mammalian cell cycle checkpoint control, inducing G1 arrest in response to DNA damage (Kuerbitz...
