Document Detail

Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers.
MedLine Citation:
PMID:  17108109     Owner:  NLM     Status:  MEDLINE    
Neuroendocrine differentiation is a common feature of lung cancer and increased numbers of neuroendocrine cells and their peptides have been described in chronic smokers. To understand the effects of cigarette smoking on the gene expression profile of neuroendocrine cells, microarray analysis with TaqMan confirmation was used to assess airway epithelial samples obtained by fiberoptic bronchoscopy from 81 individuals [normal nonsmokers, normal smokers, smokers with early chronic obstructive lung disease (COPD), and smokers with established COPD]. Of 11 genes considered to be neuroendocrine cell specific, only ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a member of the ubiquitin proteasome pathway, was consistently up-regulated in smokers compared with nonsmokers. Up-regulation of UCHL1 at the protein level was observed with immunohistochemical analysis of bronchial biopsies of smokers compared with nonsmokers. UCHL1 expression was evident only in neuroendocrine cells of the airway epithelium in nonsmokers; however, UCHL1 was also expressed in ciliated epithelial cells in smokers. This observation may add further weight to recent observations that ciliated cells are capable of transdifferentiating to other airway epithelial cells. In the context that UCHL1 is involved in the degradation of unwanted, misfolded, or damaged proteins within the cell and is overexpressed in >50% of lung cancers, its overexpression in chronic smokers may represent an early event in the complex transformation from normal epithelium to overt malignancy.
Brendan J Carolan; Adriana Heguy; Ben-Gary Harvey; Philip L Leopold; Barbara Ferris; Ronald G Crystal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  66     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2006-12-14     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10729-40     Citation Subset:  IM    
Department of Genetic Medicine and Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, New York, USA.
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MeSH Terms
Bronchi / enzymology*
Epithelium / enzymology
Gene Expression
Neurosecretory Systems / metabolism,  pathology,  physiology
Pulmonary Disease, Chronic Obstructive / enzymology,  genetics,  pathology
Reverse Transcriptase Polymerase Chain Reaction
Smoking / genetics,  metabolism*
Ubiquitin Thiolesterase / biosynthesis*,  genetics
Grant Support
Reg. No./Substance:
EC Thiolesterase; EC carboxyl-Terminal Hydrolase L-1, human

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