Cell of Origin of Small Cell Lung Cancer: Inactivation of Trp53 and Rb1 in Distinct Cell Types of Adult Mouse Lung

Cancer Cell. 2011 Jun 14;19(6):754-64. doi: 10.1016/j.ccr.2011.04.019.

Abstract

Small cell lung cancer (SCLC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we assessed the effect of Trp53 and Rb1 inactivation in distinct cell types in the adult lung using adenoviral vectors that target Cre recombinase to Clara, neuroendocrine (NE), and alveolar type 2 (SPC-expressing) cells. Using these cell type-restricted Adeno-Cre viruses, we show that loss of Trp53 and Rb1 can efficiently transform NE and SPC-expressing cells leading to SCLC, albeit SPC-expressing cells at a lesser efficiency. In contrast, Clara cells were largely resistant to transformation. The results indicate that although NE cells serve as the predominant cell of origin of SCLC a subset of SPC-expressing cells are also endowed with this ability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Cell Transformation, Neoplastic*
  • Integrases / physiology
  • Lung / pathology*
  • Lung Neoplasms / pathology*
  • Mice
  • Neuroendocrine Cells / pathology
  • Retinoblastoma Protein / physiology*
  • Small Cell Lung Carcinoma / pathology*
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Cre recombinase
  • Integrases