p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors

doi:10.1073/pnas.0602477103

p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors

*Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;
^†Department of Pathology, Stanford University, Stanford, CA 94305;
^‡Departments of Molecular and Cellular Biology and
^§Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030; and
^‖Wellcome Trust Sanger Centre, Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom

Communicated by Bruce W. Stillman, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, April 10, 2006 (received for review November 15, 2005)

Abstract

Homology between p63 and p53 has suggested that these proteins might function similarly. However, the majority of data from human tumors have not supported a similar role for p63 in tumor suppression. To investigate this issue, we studied spontaneous tumorigenesis in p63+/− mice in both WT and p53-compromised backgrounds. We found that p63+/− mice were not tumor prone and mice heterozygous for both p63 and p53 had fewer tumors than p53+/− mice. The rare tumors that developed in mice with compromised p63 were also distinct from those of p53+/− mice. Furthermore, p63+/− mice were not prone to chemically induced tumorigenesis, and p63 expression was maintained in carcinomas. These findings demonstrate that, in agreement with data from human tumors, p63 plays a markedly different biological role in cancer than p53.

Footnotes

**To whom correspondence should be addressed. E-mail: mills{at}cshl.edu
↵ ^¶Present address: Department of Radiology, Duke University, Durham, NC 27705.
Author contributions: A.B. and A.A.M. designed research; W.M.K., H.V., X.G., Y.Q., and A.A.M. performed research; W.M.K., H.V., X.G., and A.A.M. analyzed data; W.M.K., H.V., and A.A.M. wrote the paper. Specifically for experiments shown in Fig. 6, D.R.R. and A.A.M. designed research; M.I.K., K.M.P., and A.A.M. performed research; M.I.K. and K.M.P. analyzed data; and M.I.K. and A.A.M. wrote this section of the manuscript.
Conflict of interest statement: No conflicts declared.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF533892).
Abbreviations:

Abbreviations:

DBD,

DNA binding domain;

LOH,

loss of heterozygosity;

SCC,

squamous cell carcinoma.