Faculty Collaboration Database

p53 transgenic mice are highly susceptible to 1, 2-dimethylhydrazine-induced uterine sarcomas. Cancer Res 2002 Jun 01;62(11):3024-9

Date

05/31/2002

Pubmed ID

12036908

Scopus ID

2-s2.0-0036605992 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

p53 Transgenic mice were crossed with C57BL/6J mice to investigate whether a germ-line mutation in the p53 gene predisposes for tumorigenesis in mice. (C57BL/6J x UL53-3) F(1) mice were treated with 1,2-dimethylhydrazine (DMH), a colon carcinogen. The presence of a mutant p53 led to an increased incidence or multiplicity of uterine sarcomas, colon carcinomas, lung adenomas, and hepatomas in DMH-treated mice. The most significant effect of mutant p53 was the increased incidence of uterine sarcomas, which were found in approximately 90% of p53(val135/wt) mice but only seen in approximately 10% of p53(wt/wt) mice. After examination of 15 known p53 downstream target genes in uterine sarcomas and normal uteri, we found that expression of the Reprimo gene was significantly increased in normal uteri of p53(wt/wt) mice but not in either normal uterus or uterine sarcomas of p53(val135/wt) mice. In DMH-treated animals, long-term treatment with this chemopreventive agent, piroxicam, reduced colon carcinoma incidence and multiplicity in both p53(val135/wt) or p53(wt/wt) mice but did not affect the formation of uterine sarcomas, lung adenomas, or hepatomas. These results demonstrate a tissue-specific enhancement of tumorigenesis in multiple organs by the mutant p53 transgene and additionally support the utility of (C57BL/6J x UL53-3) F(1) mice for chemoprevention studies.

Author List

Zhang Z, Li J, Lantry LE, Wang Y, Wiseman RW, Lubet RA, You M

MESH terms used to index this publication - Major topics in bold

1,2-Dimethylhydrazine
Animals
Anti-Inflammatory Agents, Non-Steroidal
Carcinogens
Cell Cycle Proteins
Cocarcinogenesis
Female
Genes, p53
Genetic Predisposition to Disease
Germ-Line Mutation
Glycoproteins
Mice
Mice, Inbred C57BL
Mice, Transgenic
Piroxicam
Sarcoma
Tumor Suppressor Protein p53
Uterine Neoplasms