High metastatic potential in mice inheriting a targeted p53 missense mutation.

Content Provider	Semantic Scholar
Author	Liu, Guangzhi Mcdonnell, Timothy John Luna, R. Montes De Oca Kapoor, Mili Mims, Barbara Clark El-Naggar, Adel K. Lozano, Guillermina
Copyright Year	2000
Abstract	To understand the relevance of p53 missense mutations in vivo, we generated a mouse containing an arg-to-his substitution at p53 amino acid 172, which corresponds to the R175H hot-spot mutation in human tumors by homologous recombination. Inadvertently, this mouse contains the additional deletion of a G nucleotide at a splice junction that attenuates levels of mutant p53 to near wild-type levels. Mice heterozygous for the mutant allele differed from p53(+/-) mice in tumor spectrum, with a significant increase in the number of carcinomas and a slight decrease in the number of lymphomas. More importantly, the osteosarcomas and carcinomas that developed in these mutant mice frequently metastasized (69% and 40%, respectively). In contrast, metastasis is rare in osteosarcomas of p53(+/-) mice. Loss of heterozygosity studies of tumors indicated loss of heterozygosity in only 1 of 11 tumors. These data indicate clear differences between a p53 missense mutation and a null allele in tumorigenesis in vivo and suggest that the p53R172HDeltag mutant represents a gain-of-function allele.
File Format	PDF HTM / HTML
DOI	10.1073/pnas.97.8.4174
PubMed reference number	10760284
Journal	Medline
Volume Number	97
Issue Number	8
Alternate Webpage(s)	http://www.pnas.org/content/97/8/4174.full.pdf
Alternate Webpage(s)	https://doi.org/10.1073/pnas.97.8.4174
Journal	Proceedings of the National Academy of Sciences of the United States of America
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article