Cross-talk between aryl hydrocarbon receptor and mitogen-activated protein kinase signaling pathway in liver cancer through c-raf transcriptional regulation

Molecular Cancer Research : MCR
Jürgen Borlak, Hans Stephan Jenke

Abstract

c-raf is a serine-threonine kinase and a downstream effector of ras signaling. This kinase plays an essential role in cell proliferation, differentiation, and apoptosis. In the past, we reported induction of c-raf gene expression in rat liver cancer on treatment with a mixture of aryl hydrocarbon receptor (AhR) agonists. This prompted our interest in investigating the role of AhR in the transcriptional regulation of c-raf. Initially, we cloned the rat c-raf promoter and sequenced the genomic DNA and cDNA by Southern blotting and capillary electrophoresis. Then, a genetic algorithm was applied to search for putative AhR-binding sites. DNA-binding activity of AhR was confirmed by electromobility shift assay. We also studied c-raf gene expression in rat hepatoma cell lines with functional and/or devoid AhR and in primary human and rat hepatocyte cultures. Overall, we identified five and three AhR-binding sites in the human and rat c-raf gene, respectively. Treatment of hepatocyte cultures with the AhR antagonist resveratrol reduced DNA binding of AhR. Only rat hepatoma cells with functional AhR responded to 1 nmol/L 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment with >10-fold c-raf mRNA induction. Treatment of human and rat hepatoc...Continue Reading

References

Mar 1, 1979·Journal of Toxicology and Environmental Health·P O Seglen
Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jul 1, 1990·Molecular and Cellular Biology·T W BeckU R Rapp
Feb 1, 1989·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J C DunnR G Tompkins
Mar 1, 1987·Molecular and Cellular Biology·F IshikawaT Sugimura
Jun 1, 1994·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H S JenkeD Oesterle
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·J V SchmidtC A Bradfield
Dec 24, 1997·Genomics·W R PearsonW Miller
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y ShimizuT Ishikawa
Jan 11, 2000·Nucleic Acids Research·E WingenderS Urbach
May 31, 2002·Expert Opinion on Pharmacotherapy·Walter Kolch
Jul 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·Patrik AnderssonLorenz Poellinger
Feb 14, 2003·International Journal of Cancer. Journal International Du Cancer·Emily P SlaterRolf Müller
Mar 19, 2003·Chemical Research in Toxicology·Qiang Ma, Anthony Y H Lu
Apr 15, 2003·Toxicology and Applied Pharmacology·Jürgen BorlakElmar Richter
Jan 13, 2004·Circulation Research·Michael J Ryan, Curt D Sigmund
Mar 19, 2004·The Journal of Biological Chemistry·Daniel W NebertFrank J Gonzalez
Nov 3, 2004·Nature Reviews. Molecular Cell Biology·Claudia WellbrockRichard Marais
Apr 14, 2005·Molecular Cancer Therapeutics·Srikala S SridharLillian L Siu

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Citations

Mar 14, 2013·Archives of Toxicology·Eva ZellerAlbert Braeuning
Apr 3, 2013·Journal of Molecular Histology·Ziyu LiuZhikai Xu
Jun 17, 2009·PloS One·Astrid RohrbeckJürgen Borlak
Jul 5, 2016·Chemico-biological Interactions·Heidi Q XieBin Zhao
Jul 22, 2018·Cellular and Molecular Life Sciences : CMLS·David M DolivoTanja Dominko
Apr 10, 2017·Environmental Science and Pollution Research International·Jonas HausenRichard Ottermanns
Aug 11, 2021·Signal Transduction and Targeted Therapy·Qing ZhuYuchen Jiao

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