Document Detail

Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis.
MedLine Citation:
PMID:  23047698     Owner:  NLM     Status:  MEDLINE    
Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanisms underlying them have been elucidated. Importantly, PNECs have long been speculated to constitute the cells of origin of human small-cell lung cancer (SCLC) and recent mouse models support this hypothesis. However, a genetic system that permits tracing the early events of PNEC transformation has not been available. To address these key issues, we developed a genetic tool in mice by introducing a fusion protein of Cre recombinase and estrogen receptor (CreER) into the calcitonin gene-related peptide (CGRP) locus that encodes a major peptide in PNECs. The CGRP(CreER) mouse line has enabled us to manipulate gene activity in PNECs. Lineage tracing using this tool revealed the plasticity of PNECs. PNECs can be colabeled with alveolar cells during lung development, and following lung injury, PNECs can contribute to Clara cells and ciliated cells. Contrary to the current model, we observed that elimination of PNECs has no apparent consequence on Clara cell recovery. We also created mouse models of SCLC in which CGRP(CreER) was used to ablate multiple tumor suppressors in PNECs that were simultaneously labeled for following their fate. Our findings suggest that SCLC can originate from differentiated PNECs. Together, these studies provide unique insight into PNEC lineage and function and establish the foundation of investigating how PNECs contribute to lung homeostasis, injury/repair, and tumorigenesis.
Hai Song; Erica Yao; Chuwen Lin; Rhodora Gacayan; Miao-Hsueh Chen; Pao-Tien Chuang
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Publication Detail:
Type:  Journal Article     Date:  2012-10-09
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17531-6     Citation Subset:  IM    
Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA.
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MeSH Terms
Cell Transformation, Neoplastic
Genes, Retinoblastoma
Genes, p53
Lung / cytology*
Lung Neoplasms / pathology*
Neuroendocrine Cells / physiology*
PTEN Phosphohydrolase / genetics
Reg. No./Substance:
EC Phosphohydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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