Document Detail


Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma.
MedLine Citation:
PMID:  20658532     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent cause of cancer death in the world, and cigarette smoke is a key factor in esophageal carcinogenesis. To identify molecular changes during cigarette smoke-induced ESCC, we examined the methylation status of 13 gene promoters in the human immortalized, nontumorigenic esophageal epithelial cell line (Het-1A) that were exposed to mainstream (MSE) or sidestream cigarette smoke extract (SSE) for 6 months in culture. The promoter of sequence-specific single-stranded DNA-binding protein 2 (SSBP2) was methylated in the Het-1A cells exposed to MSE (MSE-Het-1A). Promoter methylation (86%, 56/70) and downregulation of SSBP2 expression were frequently detected in tumor tissues from ESCC patients. In addition, reintroduction of SSBP2 in an ESCC cell line (TE1) that does not express SSBP2 and in the MSE-Het-1A cells inhibited expression of LRP6 and Dvl3, which are mediators of the Wnt signaling pathway. SSBP2 expression markedly decreased the colony-forming ability of ESCC cell lines and significantly inhibited cell growth of the MSE-Het-1A cells. Our results indicate that cigarette smoking is a cause of SSBP2 promoter methylation and that SSBP2 harbors a tumor suppressive role in ESCC through inhibition of the Wnt signaling pathway.
Authors:
Yiping Huang; Xiaofei Chang; Juna Lee; Yong Gu Cho; Xiaoli Zhong; Il-Seok Park; Jun-Wei Liu; Joseph A Califano; Edward A Ratovitski; David Sidransky; Myoung Sook Kim
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  128     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-03-28     Completed Date:  2011-05-26     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2261-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 UICC.
Affiliation:
Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Squamous Cell / genetics*
Cell Line, Transformed
DNA Methylation*
DNA-Binding Proteins / genetics*
Esophageal Neoplasms / genetics*
Humans
Immunohistochemistry
Promoter Regions, Genetic*
Reverse Transcriptase Polymerase Chain Reaction
Smoke*
Tobacco*
Grant Support
ID/Acronym/Agency:
U01 CA084986/CA/NCI NIH HHS; U01 CA084986-01/CA/NCI NIH HHS; U01-CA84986/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/SSBP2 protein, human; 0/Smoke
Comments/Corrections

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