HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Impact of smoking on the expression of claudins in lung carcinoma.

AbstractRATIONALE:
Tight junctions regulate the paracellular permeability and orientation of cells and claudins are key components of tight junctions.
OBJECTIVES:
To study the influence of cigarette smoke on claudin expression in vitro and in lung cancer patients.
METHODS:
We studied the effect of smoking on claudin expression by exposing a bronchial cell line (BEAS-2B) and two carcinoma cell lines (SK-LU1 and SK-MES1) to tobacco smoke for 48 h and analysed their claudin mRNA expression. The relation between smoked pack years and protein expression of claudins 1-5 and 7 in 344 lung cancer patients was determined by immunohistochemistry.
MEASUREMENTS AND MAIN RESULTS:
In BEAS-2B cells and SK-LU1 cells, an initial increase was followed by a decline in the mRNA expression of several claudins. In SK-MES1 cells, no evident elevation in claudin expression was observed. Intense claudin 1 and 4 positivity was found more often in cancer samples of smokers and ex-smokers compared to non-smokers (p<0.001 and p=0.003, respectively). Heavy smokers with longer than 40 pack-years consumption had more often intense claudin 1 (p=0.011), 4 (p=0.050) or 7 (p=0.058) expression in squamous cell carcinoma compared to non-smokers or smokers with fewer pack-years. Claudin 1 positivity predicted a better survival in adenocarcinoma (p=0.044) and in squamous cell carcinoma (p=0.027) and claudin 4 positivity in adenocarcinoma only (p=0.048). In squamous cell carcinoma, claudin 7 positivity was associated with a better survival (p=0.011).
CONCLUSIONS:
Bronchial BEAS-2B cells and SK-LU1 cells respond to tobacco smoke by changing their claudin mRNA synthesis and resulting tight junction permeability changes may thus contribute to tobacco induced carcinogenesis both during initiation and progression. This concept is strengthened by findings in the clinical tumour material, where tobacco consumption was associated with claudin expression.
AuthorsHeta Merikallio, Riitta Kaarteenaho, Paavo Pääkkö, Siri Lehtonen, Pasi Hirvikoski, Riitta Mäkitaro, Terttu Harju, Ylermi Soini
JournalEuropean journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 47 Issue 4 Pg. 620-30 (Mar 2011) ISSN: 1879-0852 [Electronic] England
PMID21106366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Claudins
Topics
  • Aged
  • Bronchi (metabolism)
  • Carcinoma (metabolism, mortality)
  • Cell Line
  • Cell Line, Tumor
  • Claudins (metabolism)
  • Female
  • Humans
  • Lung Neoplasms (etiology, metabolism, mortality)
  • Male
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking (metabolism, mortality)
  • Tight Junctions

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: