Mouse Lung Neuroendocrine Carcinomas: Distinct Morphologies, Same Transcription Factors

Abstract

Constitutive expression of human achaete-scute homolog-1 (hASH-1) in combination with simian virus large T antigen 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 extrapulmonary 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.

Key Words:

• achaete-scute homolog-1
• Clara cell
• conditional
• lung cancer
• mouse
• neuroendocrine
• p53
• premalignant changes
• Rb-1
• transcription factors
• transgenic