Related Experiment Video

Updated: Aug 16, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

Promoter-hypermethylation is causing functional relevant downregulation of methylthioadenosine phosphorylase (MTAP)

Claus Hellerbrand1, Marcus Mühlbauer, Susanne Wallner

  • 1Department of Internal Medicine I and Institute of Pathology, University of Regensburg, D-93042 Regensburg, Germany.

Carcinogenesis
|August 6, 2005
PubMed

Insights

Methylthioadenosine phosphorylase (MTAP) is downregulated in liver cancer due to promoter hypermethylation, not gene deletion. Restoring MTAP reduces cancer invasiveness and enhances sensitivity to interferon therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The methylthioadenosine phosphorylase (MTAP) gene, located at chromosomal region 9p21, is frequently deleted in various cancers, often alongside tumor suppressor genes like p16 and p15.
  • Understanding MTAP's role in hepatocellular carcinoma (HCC) is crucial given its frequent genomic alterations in cancer.

Purpose of the Study:

  • To investigate MTAP expression in HCC.
  • To elucidate the regulatory mechanisms of MTAP in hepatocancerogenesis.
  • To determine the functional significance of MTAP downregulation in HCC development and progression.

Main Methods:

  • Real-time PCR and western blotting to assess MTAP expression in HCC cell lines and tissues.
  • Analysis of MTAP promoter methylation.
  • Stable transfection to re-express MTAP in HCC cell lines.
  • Assessment of cell proliferation and invasion assays.
  • Evaluation of interferon-induced cell proliferation inhibition.

Main Results:

  • MTAP expression was significantly downregulated in HCC cell lines and tumor tissues compared to normal liver cells and tissues.
  • Downregulation of MTAP was attributed to promoter hypermethylation, not genomic loss or mutations.
  • Re-expression of MTAP in HCC cells reduced their invasive potential but did not affect proliferation.
  • MTAP re-expressing cells showed enhanced sensitivity to interferon-alpha and interferon-gamma mediated growth inhibition.

Conclusions:

  • MTAP inactivation plays a functional role in the development and invasiveness of HCC.
  • The findings suggest MTAP's potential clinical significance in HCC therapeutic strategies, particularly concerning interferon sensitivity.

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