Journal of Biomedical Science

, Volume 12, Issue 5, pp 803–813

Epigenetic activation of α4, β2 and β6 integrins involved in cell migration in trichostatin A-treated Hep3B cells

Authors

  • Kuen-Tyng Lin
    • Graduate Institute of Life Sciences, National Defense Medical CenterNational Defense University
    • Division of Molecular and Genomic MedicineNational Health Research Institutes
    • Academia SinicaInstitute of Biomedical Sciences
  • Shiou-Hwei Yeh
    • Department of Microbiology, College of Medicine, National Taiwan University
    • Division of Molecular and Genomic MedicineNational Health Research Institutes
  • Ding-Shinn Chen
    • Hepatitis Research Center, Department of Internal Medicine, Hospital and Graduate Institute of Clinical Medicine, College of MedicineNational Taiwan University
  • Pei-Jer Chen
    • Hepatitis Research Center, Department of Internal Medicine, Hospital and Graduate Institute of Clinical Medicine, College of MedicineNational Taiwan University
    • Graduate Institute of Life Sciences, National Defense Medical CenterNational Defense University
    • Division of Molecular and Genomic MedicineNational Health Research Institutes
    • Academia SinicaInstitute of Biomedical Sciences
Article

DOI: 10.1007/s11373-005-9005-2

Cite this article as:
Lin, K., Yeh, S., Chen, D. et al. J Biomed Sci (2005) 12: 803. doi:10.1007/s11373-005-9005-2

Summary

The epigenetic modulation by histone deacetylase (HDAC) inhibitors including trichostatin A (TSA) has been known to block cell proliferation, induce apoptosis and inhibit cell migration in human cancer cells that represents the potential therapeutic agents for cancers and fibrosis. However, more than 55% of Hep3B cells remained alive after our initial study of 100 nM TSA treatment. To further study the epigenetic modulation and the biological function of newly activated genes by HDAC inhibitor involved in HCC progression and metastasis, we profiled 23 integrin genes including 15α and 8β in TSA-treated Hep3B cells. Six integrins including three down-regulated α6, α10, β8 and three significant up-regulated α4, β2, β6 integrins were revealed after semi-quantitative RT-PCR. To confirm the epigenetic modulation and explore their biological functions, we selected the three significantly up-regulated integrins for confirmation of protein up-regulation, hyperacetylated-histones by ChIP assays, and functional inhibition by specific neutralizing antibodies of integrins. Our results indicated that epigenetic modulation in TSA-treated Hep3B cells up-regulated new integrins including α4, β2 and β6 and reduced migration activities by specific neutralizing antibodies to 61.3%, 42.4% and 34.5%, respectively. Our novel findings provided a better understanding of the epigenetic modulation of integrins and suggested that targeting the epigenetic up-regulated integrins to abrogate the migration activity might be a promising strategy to prevent HCC progression.

Keywords

epigenetichepatocellular carcinomaHep3Bintegrinsmigration

Copyright information

© National Science Council Taipei 2005