Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers

Brendan J. Carolan, Adriana Heguy, Ben Gary Harvey, Philip L. Leopold, Barbara Ferris, Ronald Crystal

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)10729-10740
Number of pages12
JournalCancer Research
Volume66
Issue number22
DOIs
Publication statusPublished - 15 Nov 2006
Externally publishedYes

Fingerprint

Hydrolases
Ubiquitin
Tobacco Products
Neuroendocrine Cells
Up-Regulation
Epithelium
Chronic Obstructive Pulmonary Disease
Genes
Lung Neoplasms
Epithelial Cells
Tissue Array Analysis
Bronchoscopy
Proteasome Endopeptidase Complex
Transcriptome
Proteins
Smoking
Biopsy
Weights and Measures
Peptides
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers. / Carolan, Brendan J.; Heguy, Adriana; Harvey, Ben Gary; Leopold, Philip L.; Ferris, Barbara; Crystal, Ronald.

In: Cancer Research, Vol. 66, No. 22, 15.11.2006, p. 10729-10740.

Research output: Contribution to journalArticle

Carolan, Brendan J. ; Heguy, Adriana ; Harvey, Ben Gary ; Leopold, Philip L. ; Ferris, Barbara ; Crystal, Ronald. / Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers. In: Cancer Research. 2006 ; Vol. 66, No. 22. pp. 10729-10740.
@article{b6ef468474444cfd836d5e6d0005c3a3,
title = "Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers",
abstract = "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.",
author = "Carolan, {Brendan J.} and Adriana Heguy and Harvey, {Ben Gary} and Leopold, {Philip L.} and Barbara Ferris and Ronald Crystal",
year = "2006",
month = "11",
day = "15",
doi = "10.1158/0008-5472.CAN-06-2224",
language = "English",
volume = "66",
pages = "10729--10740",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - Up-regulation of expression of the ubiquitin carboxyl-terminal hydrolase L1 gene in human airway epithelium of cigarette smokers

AU - Carolan, Brendan J.

AU - Heguy, Adriana

AU - Harvey, Ben Gary

AU - Leopold, Philip L.

AU - Ferris, Barbara

AU - Crystal, Ronald

PY - 2006/11/15

Y1 - 2006/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33845289459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845289459&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-06-2224

DO - 10.1158/0008-5472.CAN-06-2224

M3 - Article

VL - 66

SP - 10729

EP - 10740

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 22

ER -