Unsaturated fatty acids promote hepatoma proliferation and progression through downregulation of the tumor suppressor PTEN

Manlio Vinciguerra, Fabio Carrozzino, Marion Peyrou, Sebastiano Carlone, Roberto Montesano, Roberto Benelli, Michelangelo Foti

Research output: Contribution to journalArticle

Abstract

Background/Aims: The impact of dietary fatty acids on the development of cancers is highly controversial. We recently demonstrated that unsaturated fatty acids trigger the downregulation of the tumor suppressor PTEN through an mTOR/NF-κB-dependent mechanism in hepatocytes. In this study, we investigated whether unsaturated fatty acids promote hepatoma progression by downregulating PTEN expression. Methods: The effects of fatty acids and PTEN-specific siRNAs on proliferation, invasiveness and gene expression were assessed using HepG2 hepatoma cells. The tumor promoting activity of unsaturated fatty acids was evaluated in vivo using HepG2 xenografts in nude mice. Results: Incubation of HepG2 cells with unsaturated fatty acids, or PTEN-specific siRNAs, increased cell proliferation, cell migration and invasiveness, and altered the expression of genes involved in inflammation, epithelial-to-mesenchymal transition and carcinogenesis. These effects were dependent on PTEN expression levels and were prevented by mTOR and NF-κB inhibitors. Consistent with these data, the development and size of subcutaneous HepG2-derived tumors in nude mice xenografts were dramatically increased when mice were fed with an oleic acid-enriched diet, even in the absence of weight gain. Conclusions: These data demonstrate that dietary unsaturated fatty acids promote hepatoma progression by reducing the expression of the tumor suppressor PTEN.

Original languageEnglish
Pages (from-to)1132-1141
Number of pages10
JournalJournal of Hepatology
Volume50
Issue number6
DOIs
Publication statusPublished - Jun 2009

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Keywords

  • Cancer
  • Hepatocytes
  • mTOR
  • NF-κBp65
  • PTEN
  • UFAs

ASJC Scopus subject areas

  • Hepatology

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