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Deregulation of the activin/follistatin system in hepatocarcinogenesis

Michael Grusch1, Claudia Drucker, Barbara Peter-Vörösmarty

  • 1Department of Medicine I, Division: Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. michael.grusch@meduniwien.ac.at

Journal of Hepatology
|August 29, 2006
PubMed
Abstract

Insights

Activins and follistatins regulate liver cell numbers. Their expression is disrupted in liver cancer, suggesting the activin/follistatin system as a therapeutic target for hepatocarcinogenesis.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Cancer Research

Background:

  • Activins A and E inhibit liver cell replication and promote apoptosis.
  • Follistatin and follistatin-like 3 are antagonists of activin activity.
  • The role of activins and follistatins in liver cancer (hepatocarcinogenesis) is not well understood.

Purpose of the Study:

  • To investigate the role of activins and follistatins in hepatocarcinogenesis.
  • To analyze the expression of follistatin, follistatin-like 3, and activin subunits in liver tumors.
  • To determine the effect of follistatin and activin A on hepatocyte DNA synthesis.

Main Methods:

  • Real-time PCR and immunohistochemistry were used to assess gene and protein expression in rat and human liver tumors.
  • DNA synthesis assays were performed on normal, preneoplastic, and cancerous hepatocytes.
  • Animal models of chemically induced liver tumors were utilized.

Main Results:

  • Follistatin was upregulated, while activin subunits beta(A) and beta(E) were downregulated in most liver tumors.
  • Follistatin-like 3 expression increased in malignant rat liver but decreased in human liver cancer.
  • Follistatin stimulated DNA synthesis in preneoplastic hepatocytes, whereas activin A inhibited it.

Conclusions:

  • Deregulation of the activin/follistatin system occurs during hepatocarcinogenesis.
  • Preneoplastic hepatocytes show sensitivity to activin signaling.
  • The activin/follistatin pathway represents a potential therapeutic target for liver cancer.

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