Characterization of the cell of origin for small cell lung cancer

Kwon Sik Park, Mei-Chih Liang, David M. Raiser, Raffaella Zamponi, Rebecca R. Roach, Stephen J. Curtis, Zandra Walton, Bethany E. Schaffer, Caitlin M. Roake, Anne Flore Zmoos, Christina Kriegel, Kwok Kin Wong, Julien Sage*, Carla F. Kim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Small cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer that affects more than 200,000 people worldwide every year with a very high mortality rate. Here, we used a mouse genetics approach to characterize the cell of origin for SCLC; in this mouse model, tumors are initiated by the deletion of the Rb and p53 tumor suppressor genes in the lung epithelium of adult mice. We found that mouse SCLCs often arise in the lung epithelium where neuroendocrine cells are located and that the majority of early lesions were composed of proliferating neuroendocrine cells. In addition, mice in which Rb and p53 are deleted in a variety of non-neuroendocrine lung epithelial cells did not develop SCLC. These data indicate that SCLC likely arises from neuroendocrine cells in the lung.

Original languageEnglish
Pages (from-to)2806-2815
Number of pages10
JournalCell Cycle
Issue number16
StatePublished - 15 Aug 2011


  • Cancer
  • Cell of origin
  • Lung
  • Neuroendocrine
  • Rb
  • SCLC
  • p53

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