Dietary PUFA modulate the expression of proliferation and differentiation markers in Morris 3924A hepatoma cells

Abstract: The effect of dietary polyunsaturated fatty acids on the expression of differentiation and proliferation markers in Morris 3924A hepatoma cells was investigated. ACT/I rats were conditioned 10 days with diets enriched with linoleic acid or α-linolenic acid before subcutaneous hepatoma cell transplantation. After 19 days from the inoculum, the mRNA levels of liver-enriched transcription factors and of their target genes were quantified. Both linoleic acid- and linolenic acid-enriched diets induced a decrease of β-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1α and HNF-4α mRNA levels in tumor tissue whereas HNF-3β expression was induced by both dietary treatments. Only the α-linolenic acid-enriched diet was effective in reducing c-jun and increasing albumin mRNA levels. Since albumin is a C/EBPα target gene, C/EBPα gene transcription was evaluated at both protein and mRNA levels. It was found that α-linolenic acid-enriched diet did not enhance the C/EBPα mRNA content in hepatoma tissue while inducing C/EBPα protein expression with an isoform pattern similar to the hepatic phenotype. This evidence implies that α-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by modulating C/EBPα gene expression at post-transcriptional level. [Copyright &y& Elsevier]