PMID- 10190553 OWN - NLM STAT- MEDLINE DCOM- 19990413 LR - 20231213 IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 20 IP - 3 DP - 1999 Mar TI - Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. PG - 401-6 AB - 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. FAU - Piechocki, M P AU - Piechocki MP AD - Department of Pathology, Medical College of Ohio, Toledo 43699-0008, USA. FAU - Burk, R D AU - Burk RD FAU - Ruch, R J AU - Ruch RJ LA - eng GR - CA-R29-57612/CA/NCI NIH HHS/United States GR - DK-5P30-41296/DK/NIDDK NIH HHS/United States GR - DK-P01-41918/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Cell Line MH - Connexin 43/*genetics MH - Connexins/*genetics MH - *DNA Methylation MH - Dexamethasone/pharmacology MH - Gene Expression Regulation/drug effects/*genetics MH - Liver/cytology/drug effects/*metabolism MH - Promoter Regions, Genetic MH - Rats MH - Rats, Inbred F344 MH - Transfection MH - Gap Junction beta-1 Protein EDAT- 1999/04/06 00:00 MHDA- 1999/04/06 00:01 CRDT- 1999/04/06 00:00 PHST- 1999/04/06 00:00 [pubmed] PHST- 1999/04/06 00:01 [medline] PHST- 1999/04/06 00:00 [entrez] AID - 10.1093/carcin/20.3.401 [doi] PST - ppublish SO - Carcinogenesis. 1999 Mar;20(3):401-6. doi: 10.1093/carcin/20.3.401.