Evidence for type II cells as cells of origin of K-Ras-induced distal lung adenocarcinoma

Proc Natl Acad Sci U S A. 2012 Mar 27;109(13):4910-5. doi: 10.1073/pnas.1112499109. Epub 2012 Mar 12.

Abstract

Identifying the cells of origin of lung cancer may lead to new therapeutic strategies. Previous work has focused upon the putative bronchoalveolar stem cell at the bronchioalveolar duct junction as a cancer cell of origin when a codon 12 K-Ras mutant is induced via adenoviral Cre inhalation. In the present study, we use two "knock-in" Cre-estrogen receptor alleles to inducibly express K-RasG12D in CC10(+) epithelial cells and Sftpc(+) type II alveolar cells of the adult mouse lung. Analysis of these mice identifies type II cells, Clara cells in the terminal bronchioles, and putative bronchoalveolar stem cells as cells of origin for K-Ras-induced lung hyperplasia. However, only type II cells appear to progress to adenocarcinoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Alveolar Epithelial Cells / metabolism*
  • Alveolar Epithelial Cells / pathology*
  • Animals
  • Bronchioles / metabolism
  • Bronchioles / pathology
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Green Fluorescent Proteins / metabolism
  • Hyperplasia
  • Intercellular Signaling Peptides and Proteins
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Mice
  • Models, Biological
  • Mutant Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Peptides / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Pulmonary Surfactant-Associated Protein C
  • SOXB1 Transcription Factors / metabolism
  • Time Factors
  • Transcriptome / genetics
  • Uteroglobin / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • Mutant Proteins
  • Peptides
  • Pulmonary Surfactant-Associated Protein C
  • SOXB1 Transcription Factors
  • Scgb1a1 protein, mouse
  • Sftpc protein, mouse
  • Sox2 protein, mouse
  • Green Fluorescent Proteins
  • Uteroglobin
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)