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Lung-specific expression of human mutant p53-273H is associated with a high frequency of lung adenocarcinoma in transgenic mice.

Abstract：

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Duan W,Ding H,Subler MA,Zhu WG,Zhang H,Stoner GD,Windle JJ,Otterson GA,Villalona-Calero MA

doi

10.1038/sj.onc.1205909

subject

Has Abstract

pub_date

2002-11-07 00:00:00

pages

7831-8

issue

51

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

杂志文章

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