Enhanced susceptibility to chemical induction of ovarian tumors in mice with a germ line p53 mutation. Mol Cancer Res 2008 Jan;6(1):99-109
Date
02/01/2008Pubmed ID
18234966DOI
10.1158/1541-7786.MCR-07-0216Scopus ID
2-s2.0-40749088488 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
Mice with a germ line p53 mutation (p53(Ala135Val/wt)) display increased susceptibility to lung, skin, and colon carcinogenesis. Here, we show that p53(Ala135Val/wt) mice developed ovarian tumors significantly more rapidly than their wild-type littermates after 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Approximately 50% of the ovarian tumors in p53(wt/wt) mice and 23% in p53(Ala135Val/wt) mice are adenocarcinomas and the remaining tumors were adenocarcinoma mixed with sarcoma or ovarian sarcomas. All of the p53(Ala135Val/wt) mice had died of ovarian tumors 25 weeks after the initial DMBA treatment, whereas >50% of p53(wt/wt) mice were still alive. These mice not only have a shortened tumor latency but also closely resemble a subset of human ovarian tumors containing the p53 mutation. Microarray and GenMAPP analyses revealed that the mutant p53 (Ala135Val) affected several cellular processes, including the cell cycle, apoptosis, and Wnt pathways. These findings indicate that a germ line p53 mutation significantly enhanced DMBA-induced ovarian tumor development and progression.
Author List
Wang Y, Zhang Z, Lu Y, Yao R, Jia D, Wen W, LaRegina M, Crist K, Lubet R, You MMESH terms used to index this publication - Major topics in bold
9,10-Dimethyl-1,2-benzanthraceneAnimals
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genes, Neoplasm
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Mice
Mice, Transgenic
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms
Tumor Suppressor Protein p53
