PMID- 10972973 OWN - NLM STAT- MEDLINE DCOM- 20010105 LR - 20231213 IS - 0730-2312 (Print) IS - 0730-2312 (Linking) VI - 79 IP - 3 DP - 2000 Sep 7 TI - Growth inhibition in G(1) and altered expression of cyclin D1 and p27(kip-1 )after forced connexin expression in lung and liver carcinoma cells. PG - 347-54 AB - Gap junctional intercellular communication (GJIC) and connexin expression are frequently decreased in neoplasia and may contribute to defective growth control and loss of differentiated functions. GJIC, in E9 mouse lung carcinoma cells and WB-aB1 neoplastic rat liver epithelial cells, was elevated by forced expression of the gap junction proteins, connexin43 (Cx43) and connexin32 (Cx32), respectively. Transfection of Cx43 into E9 cells increased fluorescent dye-coupling in the transfected clones, E9-2 and E9-3, to levels comparable to the nontransformed sibling cell line, E10, from which E9 cells originated. Transduction of Cx32 into WB-aB1 cells also increased dye-coupling in the clone, WB-a/32-10, to a level that was comparable to the nontransformed sibling cell line, WB-F344. The cell cycle distribution was also affected as a result of forced connexin expression. The percentage of cells in G(1)-phase increased and the percentage in S-phase decreased in E9-2 and WB-a/32-10 cells as compared to E9 and WB-aB1 cells. Concomitantly, these cells exhibited changes in G(1)-phase cell cycle regulators. E9-2 and WB-a/32-10 cells expressed significantly less cyclin D1 and more p27(kip-1) protein than E9 and WB-aB1 cells. Other growth-related properties (expression of platelet-derived growth factor receptor-beta, epidermal growth factor receptor, protein kinase C-alpha, protein kinase A regulatory subunit-Ialpha, and production of nitric oxide in response to a cocktail of pro-inflammatory cytokines) were minimally altered or unaffected. Thus, enhancement of connexin expression and GJIC in neoplastic mouse lung and rat liver epithelial cells restored G(1) growth control. This was associated with decreased expression of cyclin D1 and increased expression of p27(kip-1), but not with changes in other growth-related functions. CI - Copyright 2000 Wiley-Liss, Inc. FAU - Koffler, L AU - Koffler L AD - Department of Pathology, Medical College of Ohio, Toledo, Ohio 43699, USA. FAU - Roshong, S AU - Roshong S FAU - Kyu Park, I AU - Kyu Park I FAU - Cesen-Cummings, K AU - Cesen-Cummings K FAU - Thompson, D C AU - Thompson DC FAU - Dwyer-Nield, L D AU - Dwyer-Nield LD FAU - Rice, P AU - Rice P FAU - Mamay, C AU - Mamay C FAU - Malkinson, A M AU - Malkinson AM FAU - Ruch, R J AU - Ruch RJ LA - eng GR - CA33497/CA/NCI NIH HHS/United States GR - CA57612/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Cdkn1b protein, mouse) RN - 0 (Cdkn1b protein, rat) RN - 0 (Cell Cycle Proteins) RN - 0 (Connexins) RN - 0 (Cytokines) RN - 0 (Fluorescent Dyes) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Neoplasm Proteins) RN - 0 (Receptors, Growth Factor) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Tumor Suppressor Proteins) RN - 131461-61-5 (connexin 42) RN - 136601-57-5 (Cyclin D1) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 2.7.- (Protein Kinases) SB - IM MH - Animals MH - Carcinoma/*pathology MH - *Cell Communication MH - *Cell Cycle Proteins MH - Cell Division MH - Connexins/biosynthesis/genetics/*physiology MH - Cyclin D1/*biosynthesis/genetics MH - Cyclin-Dependent Kinase Inhibitor p27 MH - Cytokines/pharmacology MH - Diffusion MH - Fluorescent Dyes/metabolism MH - G1 Phase/*physiology MH - Gap Junctions/*physiology MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Liver Neoplasms, Experimental/*pathology MH - Lung Neoplasms/*pathology MH - Mice MH - Microtubule-Associated Proteins/*biosynthesis/genetics MH - Neoplasm Proteins/biosynthesis/genetics/*physiology MH - Nitric Oxide/biosynthesis MH - Protein Kinases/biosynthesis/genetics MH - Rats MH - Receptors, Growth Factor/biosynthesis/genetics MH - Recombinant Fusion Proteins/biosynthesis MH - Transfection MH - Tumor Cells, Cultured/drug effects/metabolism MH - *Tumor Suppressor Proteins MH - Gap Junction beta-1 Protein EDAT- 2000/09/06 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/09/06 11:00 PHST- 2000/09/06 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/09/06 11:00 [entrez] AID - 10.1002/1097-4644(20001201)79:3<347::AID-JCB10>3.0.CO;2-2 [pii] AID - 10.1002/1097-4644(20001201)79:3<347::aid-jcb10>3.0.co;2-2 [doi] PST - ppublish SO - J Cell Biochem. 2000 Sep 7;79(3):347-54. doi: 10.1002/1097-4644(20001201)79:3<347::aid-jcb10>3.0.co;2-2.