Induction of MITF expression in human cholangiocarcinoma cells and hepatocellular carcinoma cells by cyclopamine, an inhibitor of the Hedgehog signaling

Biochem Biophys Res Commun. 2016 Jan 29;470(1):144-149. doi: 10.1016/j.bbrc.2016.01.010. Epub 2016 Jan 7.

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.

Keywords: Bile duct; Cholangiocyte; Cyclopamine; Hedgehog; Hepatocyte; MITF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholangiocarcinoma / metabolism*
  • Down-Regulation / drug effects
  • Hedgehog Proteins / metabolism*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Veratrum Alkaloids / administration & dosage*

Substances

  • Hedgehog Proteins
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • Veratrum Alkaloids
  • cyclopamine