Mouse lung neuroendocrine carcinomas: distinct morphologies, same transcription factors

Exp Lung Res. 2005 Jan-Feb;31(1):37-55. doi: 10.1080/01902140490495002.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antigens, Viral, Tumor / genetics
  • Antigens, Viral, Tumor / metabolism
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / metabolism
  • Carcinoma, Neuroendocrine / secondary*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal*
  • E2F Transcription Factors
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Uteroglobin / genetics
  • Uteroglobin / metabolism

Substances

  • ASCL1 protein, human
  • Antigens, Viral, Tumor
  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • NKX2-1 protein, human
  • Nkx2-1 protein, mouse
  • Nuclear Proteins
  • SCGB1A1 protein, human
  • Scgb1a1 protein, mouse
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Uteroglobin