Document Detail


Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells.
MedLine Citation:
PMID:  10190553     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gap junction proteins (connexins) are expressed in a cell-specific manner and expression is often reduced in neoplastic cells. We investigated the mechanisms of connexin32 (Cx32) and connexin43 (Cx43) expression in hepatic cells using MH1C1 rat hepatoma cells and freshly isolated, adult rat hepatocytes that express Cx32 but not Cx43 and WB-F344 rat liver epithelial cells that express Cx43 but not Cx32. Southern blotting after DNA restriction with MspI and HpaII indicated that two MspI/HpaII restriction sites in the Cx32 promoter (positions -147 and -847) were methylated in WB-F344 cells, but not in MH1C1 cells or hepatocytes. In contrast, an MspI/HpaII restriction site in the Cx43 promoter (position -38) was methylated in MH1C1 cells, but not in WB-F344 cells or hepatocytes. Transient transfection of the cell lines with connexin promoter-luciferase constructs indicated that the Cx32 promoter was 7-fold more active in MH1C1 cells and the Cx43 promoter was 5-fold more active in WB-F344 cells. These results suggest that transcription of Cx32 and Cx43 in hepatic cells is controlled by promoter methylation and by cell-specific transcription factors. Similar mechanisms may be involved in the reduced expression of these genes frequently observed in neoplastic cells.
Authors:
M P Piechocki; R D Burk; R J Ruch
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Carcinogenesis     Volume:  20     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-13     Completed Date:  1999-04-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  401-6     Citation Subset:  IM    
Affiliation:
Department of Pathology, Medical College of Ohio, Toledo 43699-0008, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Connexin 43 / genetics*
Connexins / genetics*
DNA Methylation*
Dexamethasone / pharmacology
Gene Expression Regulation / drug effects,  genetics*
Liver / cytology,  drug effects,  metabolism*
Promoter Regions, Genetic
Rats
Rats, Inbred F344
Transfection
Grant Support
ID/Acronym/Agency:
CA-R29-57612/CA/NCI NIH HHS; DK-5P30-41296/DK/NIDDK NIH HHS; DK-P01-41918/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Connexin 43; 0/Connexins; 0/connexin 32; 50-02-2/Dexamethasone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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