Induction of Small Cell Lung Cancer by Somatic Inactivation of Both Trp53 and Rb1 in a Conditional Mouse Model

Cancer Cell. 2003 Sep;4(3):181-9. doi: 10.1016/s1535-6108(03)00220-4.

Abstract

Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Carcinoma, Small Cell / etiology
  • Carcinoma, Small Cell / genetics*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, p53 / genetics*
  • Genes, p53 / physiology
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Mice
  • Mice, Transgenic
  • Retinoblastoma Protein / genetics*
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Ascl1 protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • Tumor Suppressor Protein p53