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

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.