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

Autor: Roberto Benelli, Fabio Carrozzino, Roberto Montesano, Manlio Vinciguerra, Marion Peyrou, Sebastiano Carlone, Michelangelo Foti
Rok vydání: 2009
Předmět:
Fatty Acids
Unsaturated/toxicity
Down-Regulation/drug effects
Apoptosis
medicine.disease_cause
Recombinant Fusion Proteins/genetics/metabolism
Cell Proliferation/drug effects
Mice
Liver Neoplasms
Experimental
Risk Factors
RNA
Small Interfering
RNA
Small Interfering/genetics
Cell migration
Transfection
Fatty Acids
Unsaturated
PTEN Phosphohydrolase/antagonists & inhibitors/genetics/metabolism
Cell Survival/drug effects
medicine.medical_specialty
Cell Survival
Recombinant Fusion Proteins
Transplantation
Heterologous
Down-Regulation
Mice
Nude
Biology
Downregulation and upregulation
Cell Line
Tumor
Internal medicine
medicine
Animals
Humans
PTEN
ddc:612
Hepatocytes/drug effects/metabolism/pathology
PI3K/AKT/mTOR pathway
Unsaturated fatty acid
Cell Proliferation
DNA Primers
DNA Primers/genetics
Base Sequence
Hepatology
Cell growth
Apoptosis/drug effects
PTEN Phosphohydrolase
Endocrinology
Liver Neoplasms
Experimental/etiology/genetics/pathology
Carcinogens
Hepatocytes
Cancer research
biology.protein
Carcinogenesis
Carcinogens/toxicity
Neoplasm Transplantation
Zdroj: Journal of Hepatology, Vol. 50, No 6 (2009) pp. 1132-41
ISSN: 0168-8278
DOI: 10.1016/j.jhep.2009.01.027
Popis: 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-kappaB-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-kappaB 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.
Databáze: OpenAIRE
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