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Exp Lung Res. 2005 Jan-Feb;31(1):37-55.

Mouse lung neuroendocrine carcinomas: distinct morphologies, same transcription factors.

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Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20850, USA.


Constitutive expression of human achaete-scute homolog-1 (hASH-1) in combination with simian virus large Tantigen under the Clara cell 10-kDa secretory protein (CC10) promoter results in adenocarcinomas with focal neuroendocrine (NE) differentiation. Mice carrying conditional alleles for both Rb-1 and p53 in lung epithelial cells develop aggressive lung tumors with similarities to human small cell lung cancers, including high level expression of ASH-1, NE markers, and extra-pulmonary metastases. Tumors in both models originate from bronchiolar epithelium, reveal a range of premalignant changes, express thyroid transcription factor-1 (TTF-1), a marker of peripheral airway cell lineage, and display varying degrees of bidirectional epithelial/NE differentiation.

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