| Inhibition of intrinsic gap-junction intercellular communication and enhancement of tumorigenicity of the rat bladder carcinoma cell line BC31 by a dominant-negative connexin 43 mutant. | |
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MedLine Citation:
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PMID: 9869455 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The tumor-suppressive property of the connexin gap-junction proteins was postulated from the fact that their function of cell coupling is impaired in most cancer cells. However, in conflict with this notion, certain cancer cells are able to communicate through gap junctions despite their malignancy. To explain this phenomenon, we studied by using a dominant-negative strategy the effect on tumorigenicity of loss of intrinsic gap-junction intercellular communication (GJIC) in the rat bladder carcinoma cell line BC31, which shows both expression of connexin 43 (Cx43) and intercellular communication. In cells transfected with a mutant Cx43 with seven residues deleted from the internal loop at positions 130-136 (Cx43delta), transport of the resulting connexin protein to the plasma membrane occurred normally, but the GJIC of the cells was effectively abolished at the level of permeability of established gap junctions. Dominant-negative inhibition of GJIC by Cx43delta accelerated growth of BC31 cells in nude mice. In contrast, when GJIC in BC31 cells was artificially enforced by transfection of wild-type Cx43, the cells lost the capacity to grow in vivo. Decreased phosphorylation of Cx43delta suggested close interaction of the internal loop of connexin with its commonly phosphorylated domains in the C-terminal tail and involvement of this interaction in gap-junction permeability. Therefore, we conclude that the intrinsic GJIC observed in cancer cells should be considered a tumor-suppressor factor and that its level may influence malignant growth capacity. |
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Authors:
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V A Krutovskikh; H Yamasaki; H Tsuda; M Asamoto |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular carcinogenesis Volume: 23 ISSN: 0899-1987 ISO Abbreviation: Mol. Carcinog. Publication Date: 1998 Dec |
Date Detail:
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Created Date: 1999-01-06 Completed Date: 1999-01-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8811105 Medline TA: Mol Carcinog Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 254-61 Citation Subset: IM |
Affiliation:
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International Agency for Research on Cancer, Lyon, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Carcinoma, Transitional Cell / genetics*, pathology Cell Communication / genetics* Coloring Agents / metabolism Connexin 43 / chemistry, genetics*, physiology Gap Junctions / physiology* Genes, Dominant Isoquinolines / metabolism Mice Mice, Nude Mutagenesis, Site-Directed Neoplasm Proteins / chemistry, genetics*, physiology Neoplasm Transplantation Protein Conformation Rats Recombinant Fusion Proteins / physiology Transfection Tumor Cells, Cultured Urinary Bladder Neoplasms / genetics*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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2R01 CA 40534-10A2/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Coloring Agents; 0/Connexin 43; 0/Isoquinolines; 0/Neoplasm Proteins; 0/Recombinant Fusion Proteins; 77944-88-8/lucifer yellow |
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