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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Retinoic Acid Receptor β Hypermethylation through DNA Methyltransferase 1 Accumulation in Esophageal Squamous Epithelial Cells.
MedLine Citation:
PMID:  22901195     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of RARβ. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor β (RARβ). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of RARβ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)- 2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het- 1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of RARβ in esophageal SCC patients. NNK could induce RARβ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.
Authors:
Jing Wang; Shu-Lei Zhao; Yan Li; Mei Meng; Cheng-Yong Qin
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Asian Pacific journal of cancer prevention : APJCP     Volume:  13     ISSN:  1513-7368     ISO Abbreviation:  Asian Pac. J. Cancer Prev.     Publication Date:  2012  
Date Detail:
Created Date:  2012-08-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130625     Medline TA:  Asian Pac J Cancer Prev     Country:  Thailand    
Other Details:
Languages:  eng     Pagination:  2207-12     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, China E-mail : qinchengyongjinan@gmail.com.
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