Journal
CELL CYCLE
Volume 10, Issue 16, Pages 2806-2815Publisher
LANDES BIOSCIENCE
DOI: 10.4161/cc.10.16.17012
Keywords
Rb; p53; SCLC; cell of origin; cancer; lung; neuroendocrine
Categories
Funding
- American Lung Association [NCI CA140594]
- Parker B. Francis Fellowship Program
- Damon Runyon Cancer Research Foundation
- American Cancer Society [RSG-10-071-TBG, RSG-08-082-01-MGO]
- National Institute of Health [RO1 HL090136, U01 HL100402]
- Harvard Stem Cell Institute
- United Against Lung Cancer
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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.
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