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Development of pulmonary bronchiolo-alveolar adenocarcinomas in transgenic mice overexpressing murine c-myc and epidermal growth factor in alveolar type II pneumocytes

: Ehrhardt, A.; Bartels, T.; Geick, A.; Klocke, R.; Paul, D.; Halter, R.


The British journal of cancer 84 (2001), No.6, pp.813-818
ISSN: 0007-0920
Journal Article
Fraunhofer ITA ( ITEM) ()
adenocarcinomas; Alveolar type II pneumocytes; c-myc; lung; pulmonary surfactant

Transgenic mouse models were established to study tumorigenesis of bronchiolo-alveolar adenocarcinomas derived from alveolar type IIpneumocytes (AT-II cells). Transgenic lines expressing the murineoncogene 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), astructural and functional homologue of transforming growth factor [Alpha](TGF[Alpha]), developed hyperplasias of the alveolar epithelium. Sincethe oncogenes c-myc and TGF[Alpha] are frequently overexpressed in human lung bronchiolo-alveolar adenocarcinomas, these mouse lines areuseful as models for human lung bronchiolo-alveolar adenocarcinomas. The average life expectancies of hemizygous and homozygous c- myctransgenics 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.