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 alpha-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 beta-actin, AFP, PCNA, c-myc and of hepatocyte nuclear factors HNF-1alpha and HNF-4alpha mRNA levels in tumor tissue whereas HNF-3beta expression was induced by both dietary treatments. Only the alpha-linolenic acid-enriched diet was effective in reducing c-jun and increasing albumin mRNA levels. Since albumin is a C/EBPalpha target gene, C/EBPalpha gene transcription was evaluated at both protein and mRNA levels. It was found that alpha-linolenic acid-enriched diet did not enhance the C/EBPalpha mRNA content in hepatoma tissue while inducing C/EBPalpha protein expression with an isoform pattern similar to the hepatic phenotype. This evidence implies that alpha-linolenic acid or one of its metabolic products induce albumin synthesis in hepatoma cells by modulating C/EBPalpha gene expression at post-transcriptional level.
Vecchini
Alba
A
Department of Internal Medicine, Section of Biochemistry, University of Perugia, Via del Giochetto, 3, 06126 Perugia, Italy.
Ceccarelli
Veronica
V
Nocentini
Giuseppe
G
Riccardi
Carlo
C
Di Nardo
Paolo
P
Binaglia
Luciano
L
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005227:Fatty Acids / Q000032:analysis; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage*; D015870:Gene Expression; D008055:Lipids / Q000737:chemistry; D008114:Liver Neoplasms, Experimental / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011912:Rats, Inbred ACI; D014157:Transcription Factors / Q000235:genetics
D014408:Biomarkers, Tumor; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008055:Lipids; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors