Lung-specific expression of human mutant p53-273H is associated with a high frequency of lung adenocarcinoma in transgenic mice. Oncogene 2002 Nov 07;21(51):7831-8
Date
11/07/2002Pubmed ID
12420220DOI
10.1038/sj.onc.1205909Scopus ID
2-s2.0-0037038671 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
To investigate the tumorigenic potential of mutant p53 when selectively expressed in lung tissue, a transgenic mouse model was developed in which a mutant form of p53 (p53-273H) was placed under the transcriptional control of the lung-specific human surfactant protein C (SP-C) promoter. Two founder mice were identified, and a line of SP-C/p53-273H transgenic mice was established from one of the founders. Human p53-273H protein was detected specifically in lung tissue from transgenic mice. Malignant tumors, which were histologically characterized as adenocarcinomas, were observed in transgenic mice, with the earliest onset documented at 4 months of age. To further evaluate incidence and onset of tumor formation, transgenic mice (n=113) were sacrificed at age intervals ranging from 4-15 months. At 13-15 months of age, transgenic mice were significantly more likely to have lung tumors at necropsy than age-matched non-transgenic littermates (9 out of 39 (23%) versus 2 out of 35 (5.7%), chi(2) test, P=0.036). The SP-C/p53-273H transgenic mice described here thus represent a genetically defined model with which to study the role of p53 mutations in lung tumorigenesis, as well as the potential complementary contributions of other genetic alterations or environmental carcinogens to lung tumor development.
Author List
Duan W, Ding H, Subler MA, Zhu WG, Zhang H, Stoner GD, Windle JJ, Otterson GA, Villalona-Calero MAMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAge of Onset
Amino Acid Substitution
Animals
Cell Transformation, Neoplastic
Female
Gene Expression Profiling
Genes, p53
Humans
Lung
Lung Neoplasms
Male
Mice
Mice, Transgenic
Mutation, Missense
Organ Specificity
Point Mutation
Promoter Regions, Genetic
Pulmonary Surfactant-Associated Protein C
RNA, Messenger
Recombinant Fusion Proteins
Species Specificity
Tumor Suppressor Protein p53
