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. 2001 Mar;84(6):813–818. doi: 10.1054/bjoc.2000.1676

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

A Ehrhardt 1,2, T Bartels 3, A Geick 1,4, R Klocke 1,5, D Paul 1,5, R Halter 1
PMCID: PMC2363807  PMID: 11259097

Abstract

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 α (TGFα), developed hyperplasias of the alveolar epithelium. Since the oncogenes c- myc and TGFα 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. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: c-myc, alveolar type II pneumocytes, adenocarcinoma

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Selected References

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