Document Detail

An achaete-scute homologue essential for neuroendocrine differentiation in the lung.
MedLine Citation:
PMID:  9126746     Owner:  NLM     Status:  MEDLINE    
In Drosophila and in vertebrates, the achaete-scute family of basic helix-loop-helix transcription factors plays a critical developmental role in neuronal commitment and differentiation. Relatively little is known, however, about the transcriptional control of neural features in cells outside a neuronal context. A minority of normal bronchial epithelial cells and many lung cancers, especially small-cell lung cancer, exhibit a neuroendocrine phenotype that may reflect a common precursor cell population. We show here that human achaete-scute homologue-1 (hASH1) is selectively expressed in normal fetal pulmonary neuroendocrine cells, as well as in the diverse range of lung cancers with neuroendocrine features. Strikingly, newborn mice bearing a disruption of the ASH1 gene have no detectable pulmonary neuroendocrine cells. Depletion of this transcription factor from lung cancer cells by antisense oligonucleotides results in a significant decrease in the expression of neuroendrocrine markers. Thus, a homologue of Drosophila neural fate determination genes seems to be necessary for progression of lung epithelial cells through a neuroendocrine differentiation pathway that is a feature of small-cell lung cancer, the most lethal form of human lung cancer.
M Borges; R I Linnoila; H J van de Velde; H Chen; B D Nelkin; M Mabry; S B Baylin; D W Ball
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature     Volume:  386     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  852-5     Citation Subset:  IM    
The Oncology Center, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
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MeSH Terms
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors
Cell Differentiation / physiology
DNA-Binding Proteins / genetics,  physiology*
Gene Expression
Lung / cytology*,  embryology,  innervation
Lung Neoplasms / genetics,  pathology
Mice, Transgenic
Neurosecretory Systems / cytology
Transcription Factors / genetics,  physiology*
Tumor Cells, Cultured
Reg. No./Substance:
0/ASCL1 protein, human; 0/Ascl1 protein, mouse; 0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA-Binding Proteins; 0/Transcription Factors

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