Global gene repression in hepatocellular carcinoma and fetal liver, and suppression of dudulin-2 mRNA as a possible marker for the cirrhosis-to-tumor transition

• Published in: Journal of hepatology 2005-06, Vol.42 (6), p.860-869
• Main Authors: Coulouarn, Cédric, Derambure, Céline, Lefebvre, Grégory, Daveau, Romain, Hiron, Martine, Scotte, Michel, François, Arnaud, Daveau, Maryvonne, Salier, Jean-Philippe
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Binding Sites - genetics; Biochemistry, Molecular Biology; Biological and medical sciences; Biomarkers, Tumor - genetics; Cancer; Carcinoma, Hepatocellular - genetics; Cell Cycle Proteins; Development; Down-Regulation - genetics; Dudulin-2; Female; Fetal liver; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Genomics; Hepatocyte; Humans; Life Sciences; Liver - embryology; Liver - physiology; Liver Cirrhosis - genetics; Liver Neoplasms - genetics; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Microarray; Middle Aged; Oligonucleotide Array Sequence Analysis; Oncogene Proteins - genetics; Other diseases. Semiology; Oxidoreductases; Protein function; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; Transcription factor; Transcriptome; Tumors
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.01.027

Whether the transcriptional reprogramming process induced by hepatocellular carcinoma recapitulates that of the developing liver is at present unclear. With a complete coverage of the liver transcriptome by microarray using adult livers as controls, we searched for similarities and differences in mRNA abundances between hepatocellular carcinoma nodules and fetal livers taken before (early) or after (late) the 22–24th week of gestation. Changes in some mRNA levels were studied in further liver samples by quantitative RT-PCR. Altered gene expression in hepatocellular carcinoma mostly results in down-regulated mRNAs which largely overlap with those repressed in the late fetal liver. Different frequencies of transcription factor binding sites in the down-regulated genes vs control genes as well as changes in abundance of mRNAs for relevant transcription factors point to a transcriptional repression. The down-regulated mRNAs code for proteins involved in (i) transcription and translation, (ii) specific functions of the differentiated hepatocyte or (iii) activation of proliferation and apoptosis. Apoptosis limitation is likely to predominate over active proliferation during liver development and hepatocellular carcinoma. Repression of the apoptosis-associated dudulin-2 mRNA points to a potential marker for the transition from a carcinoma-free to carcinoma-associated cirrhosis.