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@article{962162, author = {Procházková, Jiřina and Kabátková, Markéta and Bryja, Vítězslav and Umannová, Lenka and Bernatík, Ondřej and Kozubík, Alois and Machala, Miroslav and Vondráček, Jan}, article_number = {2}, doi = {http://dx.doi.org/10.1093/toxsci/kfr129}, keywords = {Wnt signaling; dioxin; intercellular junctions; contact inhibition; liver progenitor cells; differentiation}, language = {eng}, issn = {1096-6080}, journal = {Toxicological sciences}, title = {The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors.}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21602191}, volume = {122}, year = {2011} }
TY - JOUR ID - 962162 AU - Procházková, Jiřina - Kabátková, Markéta - Bryja, Vítězslav - Umannová, Lenka - Bernatík, Ondřej - Kozubík, Alois - Machala, Miroslav - Vondráček, Jan PY - 2011 TI - The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors. JF - Toxicological sciences VL - 122 IS - 2 SP - 349-360 EP - 349-360 SN - 10966080 KW - Wnt signaling KW - dioxin KW - intercellular junctions KW - contact inhibition KW - liver progenitor cells KW - differentiation UR - http://www.ncbi.nlm.nih.gov/pubmed/21602191 L2 - http://www.ncbi.nlm.nih.gov/pubmed/21602191 N2 - beta-catenin is a key integrator of cadherin-mediated cell-cell adhesion and transcriptional regulation through the Wnt/beta-catenin pathway, which plays an important role in liver biology. Using a model of contact-inhibited liver progenitor cells, we examined the interactions of Wnt/beta-catenin signaling with the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, which mediates the toxicity of dioxin-like compounds, including their effects on development and hepatocarcinogenesis. We found that AhR and Wnt/beta-catenin cooperated in the induction of AhR transcriptional targets, such as Cyp1a1 and Cyp1b1. However, simultaneously, the activation of AhR led to a decrease of dephosphorylated active beta-catenin pool, as well as to hypophosphorylation of Dishevelled, participating in regulation of Wnt signaling. A sustained AhR activation by its model ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), led to a downregulation of a number of Wnt/beta-catenin pathway target genes. TCDD also induced a switch in cytokeratin expression, where downregulation of cytokeratins 14 and 19 was accompanied with an increased cytokeratin 8 expression. Together with a downregulation of additional markers associated with stem-like phenotype, this indicated that the AhR activation interfered with differentiation of liver progenitors. ER -
PROCHÁZKOVÁ, Jiřina, Markéta KABÁTKOVÁ, Vítězslav BRYJA, Lenka UMANNOVÁ, Ondřej BERNATÍK, Alois KOZUBÍK, Miroslav MACHALA a Jan VONDRÁČEK. The interplay of the aryl hydrocarbon receptor and beta-catenin alters both AhR-dependent transcription and Wnt/beta catenin signaling in liver progenitors. \textit{Toxicological sciences}. 2011, roč.~122, č.~2, s.~349-360. ISSN~1096-6080. Dostupné z: https://dx.doi.org/10.1093/toxsci/kfr129.
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