Aryl hydrocarbon receptor-mediated disruption of contact inhibition is associated with connexin43 downregulation and inhibition of gap junctional intercellular communication
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Benz(a)Anthracenes toxicity MeSH
- Cell Line MeSH
- Time Factors MeSH
- Down-Regulation MeSH
- Epithelial Cells drug effects metabolism pathology MeSH
- Phloroglucinol analogs & derivatives pharmacology MeSH
- Fluorenes toxicity MeSH
- Phosphorylation MeSH
- Gene Knockdown Techniques MeSH
- Indoles pharmacology MeSH
- Liver drug effects metabolism pathology MeSH
- Carcinogens toxicity MeSH
- Connexin 43 genetics metabolism MeSH
- Contact Inhibition drug effects MeSH
- Rats MeSH
- Ligands MeSH
- Gap Junctions drug effects metabolism pathology MeSH
- Cell Communication drug effects MeSH
- Cell Transformation, Neoplastic chemically induced metabolism pathology MeSH
- Liver Neoplasms chemically induced metabolism pathology MeSH
- Polychlorinated Dibenzodioxins toxicity MeSH
- Cell Proliferation MeSH
- Proteasome Endopeptidase Complex metabolism MeSH
- Receptors, Aryl Hydrocarbon agonists genetics metabolism MeSH
- RNA Interference MeSH
- Signal Transduction drug effects MeSH
- Transfection MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- benz(a)anthracene MeSH Browser
- Benz(a)Anthracenes MeSH
- benzo(b)fluoranthene MeSH Browser
- Phloroglucinol MeSH
- fluoranthene MeSH Browser
- Fluorenes MeSH
- Gja1 protein, rat MeSH Browser
- IC 261 MeSH Browser
- Indoles MeSH
- Carcinogens MeSH
- Connexin 43 MeSH
- Ligands MeSH
- Polychlorinated Dibenzodioxins MeSH
- Proteasome Endopeptidase Complex MeSH
- Receptors, Aryl Hydrocarbon MeSH
The aryl hydrocarbon receptor (AhR) contributes to the control of cell-to-cell communication, cell adhesion, migration or proliferation. In the present study, we investigated the regulation of connexin43 (Cx43) and Cx43-mediated gap junctional intercellular communication (GJIC) during the AhR-dependent disruption of contact inhibition in non-tumorigenic liver epithelial cells. The contact inhibition of cell proliferation is a process restricting the cell division of confluent non-transformed cells, which is frequently abolished in cancer cells; however, the mechanisms contributing to its disruption are still only partially understood. Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced Cx43 protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner. Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by TCDD, siRNA-mediated Cx43 knock-down was not sufficient to stimulate proliferation in contact-inhibited cells. Our data suggest that downregulation of Cx43/GJIC in non-transformed epithelial cells is an inherent part of disruption of contact inhibition, which occurs at the post-transcriptional level. This process runs in parallel with alterations of other forms of cell-to-cell communication, thus suggesting that toxic AhR agonists may simultaneously abrogate contact inhibition and reduce GJIC, two essential mechanisms linked to deregulation of cell-to-cell communication during tumor promotion and progression.
References provided by Crossref.org
Applicability of Scrape Loading-Dye Transfer Assay for Non-Genotoxic Carcinogen Testing
