Stat3 Activity Is Required for Gap Junctional Permeability in Normal Rat Liver Epithelial Cells

Mulu Geletu, Chrystele Chaize, Rozanne Arulanandam, Adina Vultur, Claudia Kowolik, Aikaterini Anagnostopoulou, Richard Jove and Leda Raptis 2009. Stat3 Activity Is Required for Gap Junctional Permeability in Normal Rat Liver Epithelial Cells. DNA and Cell Biology. 28 (7), pp. 319-327. https://doi.org/10.1089/dna.2008.0833

TitleStat3 Activity Is Required for Gap Junctional Permeability in Normal Rat Liver Epithelial Cells
TypeJournal article
AuthorsMulu Geletu, Chrystele Chaize, Rozanne Arulanandam, Adina Vultur, Claudia Kowolik, Aikaterini Anagnostopoulou, Richard Jove and Leda Raptis
Abstract

Neoplastic transformation by oncogenes such as activated Src is known to suppress gap junctional, intercellular communication (GJIC). One of the Src effector pathways leading to GJIC suppression and transformation is the Ras/Raf/Mek/Erk, so that inhibition of this pathway in vSrc-transformed cells restores GJIC. A distinct Src downstream effector required for neoplasia is the signal transducer and activator of transcription-3 (Stat3). To examine the role of Stat3 upon the Src-mediated, GJIC suppression, Stat3 was downregulated in rat liver epithelial cells expressing activated Src through treatment with the CPA7, Stat3 inhibitor, or through infection with a retroviral vector expressing a Stat3-specific shRNA. GJIC was examined by electroporating the fluorescent dye, Lucifer yellow, into cells grown on two coplanar electrodes of electrically conductive, optically transparent, indium-tin oxide, followed by observation of the migration of the dye to the adjacent, nonelectroporated cells under fluorescence illumination. The results demonstrate that, contrary to inhibition of the Ras pathway, Stat3 inhibition in cells expressing activated Src does not restore GJIC. On the contrary, Stat3 inhibition in normal cells with high GJIC levels eliminated junctional permeability. Therefore, Stat3's function is actually required for the maintenance of junctional permeability, although Stat3 generally promotes growth and in an activated form can act as an oncogene.

JournalDNA and Cell Biology
Journal citation28 (7), pp. 319-327
ISSN1044-5498
1557-7430
Year2009
PublisherMary Ann Liebert
Digital Object Identifier (DOI)https://doi.org/10.1089/dna.2008.0833
Web address (URL)http://dx.doi.org/10.1089/dna.2008.0833
Publication dates
Published23 Jun 2009

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