First Author | Ehrhardt A | Year | 2001 |
Journal | Br J Cancer | Volume | 84 |
Issue | 6 | Pages | 813-8 |
PubMed ID | 11259097 | Mgi Jnum | J:68445 |
Mgi Id | MGI:1932709 | Doi | 10.1054/bjoc.2000.1676 |
Citation | Ehrhardt A, et al. (2001) Development of pulmonary bronchiolo-alveolar adenocarcinomas in transgenic mice overexpressing murine c-myc and epidermal growth factor in alveolar type II pneumocytes. Br J Cancer 84(6):813-8 |
abstractText | Transgenic mouse models were established to study tumorigenesis of bronchiolo-alveolar adenocarcinomas derived from alveolar type II pneumocytes (AT-II cells). Transgenic lines expressing the murine oncogene c- myc under the control of the lung-specific surfactant protein C promoter developed multifocal bronchiolo-alveolar hyperplasias, adenomas and carcinomas respectively, whereas transgenic lines expressing a secretable form of the epidermal growth factor (IgEGF), a structural and functional homologue of transforming growth factor alpha (TGF alpha), developed hyperplasias of the alveolar epithelium. Since the oncogenes c- myc and TGF alpha are frequently overexpressed in human lung bronchiolo-alveolar adenocarcinomas, these mouse lines are useful as models for human lung bronchiolo-alveolar adenocarcinomas. The average life expectancies of hemizygous and homozygous c- myc transgenics were 14.25 months and 9.2 months, respectively, suggesting that a dosage effect of c- myc caused an accelerated bronchiolo-alveolar adenocarcinoma formation. First analyses of double transgenics, hemizygous for both c- myc and IgEGF, show that these mice develop bronchiolo-alveolar adenocarcinomas at the average age of 9 months, indicating that these oncogenes cooperate during the lung cancer formation. Our results demonstrate that c- myc and EGF are directly involved and cooperate with one another during formation of bronchiolo-alveolar adenocarcinomas in the lung. Copyright 2001 Cancer Research Campaign |