title: Induction of MITF expression in human cholangiocarcinoma cells and hepatocellular carcinoma cells by cyclopamine, an inhibitor of the Hedgehog signaling.
abstract: Microphthalmia-associated transcription factor (MITF) is a key regulator of differentiation of melanocytes and retinal pigment epithelial cells, but it also has functions in non-pigment cells. MITF consists of multiple isoforms, including widely expressed MITF-A and MITF-H. In the present study, we explored the potential role played by the Hedgehog signaling on MITF expression in two common types of primary liver cancer, using human cholangiocarcinoma cell lines, the KKU-100 and HuCCT1, along with the HepG2 human hepatocellular carcinoma cell line. Importantly, cholangiocarcinoma is characterized by the activated Hedgehog signaling. Here we show that MITF-A mRNA is predominantly expressed in all three human liver cancer cell lines examined. Moreover, cyclopamine, an inhibitor of the Hedgehog signalling, increased the expression levels of MITF proteins in HuCCT1 and HepG2 cells, but not in KKU-100 cells, suggesting that MITF expression may be down-regulated in some liver cancer cases.
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan; Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Papavee
authors.initials: P
authors.lastname: Samatiwat
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan. Electronic address: ktakeda@med.tohoku.ac.jp.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan; Centre for Kidney Disease Research, Translational Research Institute, The University of Queensland School of Medicine, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohba
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Veerapol
authors.initials: V
authors.lastname: Kukongviriyapan
authors.affiliation: Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shibahara
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000008:administration & dosage*
chemical_list: D053823:Hedgehog Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D014704:Veratrum Alkaloids; C000541:cyclopamine
keywords: Bile duct; Cholangiocyte; Cyclopamine; Hedgehog; Hepatocyte; MITF