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Aryl hydrocarbon receptor negatively regulates expression of the plakoglobin gene (jup).
- Source :
-
Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2013 Aug; Vol. 134 (2), pp. 258-70. Date of Electronic Publication: 2013 May 20. - Publication Year :
- 2013
-
Abstract
- Plakoglobin is an important component of intercellular junctions, including both desmosomes and adherens junctions, which is known as a tumor suppressor. Although mutations in the plakoglobin gene (Jup) and/or changes in its protein levels have been observed in various disease states, including cancer progression or cardiovascular defects, the information about endogenous or exogenous stimuli orchestrating Jup expression is limited. Here we show that the aryl hydrocarbon receptor (AhR) may regulate Jup expression in a cell-specific manner. We observed a significant suppressive effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a model toxic exogenous activator of the AhR signaling, on Jup expression in a variety of experimental models derived from rodent tissues, including contact-inhibited rat liver progenitor cells (where TCDD induces cell proliferation), rat and mouse hepatoma cell models (where TCDD inhibits cell cycle progression), cardiac cells derived from the mouse embryonic stem cells, or cardiomyocytes isolated from neonatal rat hearts. The small interfering RNA (siRNA)-mediated knockdown of AhR confirmed its role in both basal and TCDD-deregulated Jup expression. The analysis of genomic DNA located ~2.5kb upstream of rat Jup gene revealed a presence of evolutionarily conserved AhR binding motifs, which were confirmed upon their cloning into luciferase reporter construct. The siRNA-mediated knockdown of Jup expression affected both proliferation and attachment of liver progenitor cells. The present data indicate that the AhR may contribute to negative regulation of Jup gene expression in rodent cellular models, which may affect cell adherence and proliferation.
- Subjects :
- Animals
Base Sequence
Cell Adhesion
Cell Line
Cell Proliferation
Cloning, Molecular
DNA Primers
Down-Regulation
Polychlorinated Dibenzodioxins pharmacology
Promoter Regions, Genetic
Rats
Rats, Inbred F344
Real-Time Polymerase Chain Reaction
Gene Expression Regulation physiology
Receptors, Aryl Hydrocarbon physiology
gamma Catenin genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0929
- Volume :
- 134
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Toxicological sciences : an official journal of the Society of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 23690540
- Full Text :
- https://doi.org/10.1093/toxsci/kft110