Positive and negative regulations of albumin gene expression by retinoids in human hepatoma cell lines.
All-trans-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (designated "acyclic retinoid") induced upregulation of the albumin gene expression at its transcriptional level, whereas all-trans-retinoic acid (RA) induced downregulation of the expression in both PLC/PRF/5 and HuH7 human hepatoma cell lines. These up- and down regulations of the albumin gene expression coordinated with high and low levels of mRNA for hepatocyte nuclear factor-1 (HNF-1), which is one of the most potent transcription factors for the albumin gene, implying that retinoids may regulate albumin gene expression through HNF-1 expression in opposite ways. The PLC/PRF/5 and HuH7 hepatoma cell lines expressed retinoid X receptor-alpha (RXR alpha) mRNA, whose expression was constitutive. Acyclic retinoid and all-trans-RA both induced upregulation of retinoic acid receptor-beta (RAR beta), and both suppressed cell proliferation-related phenotypic expressions by the alpha-fetoprotein gene and the c-myc oncogene. 9-cis-RA, whose receptor is known to be RXR alpha, also induced upregulation of albumin and HNF-1 expression. These results suggest that acyclic retinoid may act through both RXR alpha and RAR beta, whereas all-trans-RA conveys only RAR beta-mediated functions, at least in these two hepatoma cell lines.
Yamada
Y
Y
First Department of Internal Medicine, Gifu University School of Medicine, Japan.
Shidoji
Y
Y
Fukutomi
Y
Y
Ishikawa
T
T
Kaneko
T
T
Nakagama
H
H
Imawari
M
M
Moriwaki
H
H
Muto
Y
Y
D000418:Albumins / Q000235:genetics*; D016632:Apolipoprotein A-I / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016259:Genes, myc; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D009687:Nuclear Proteins; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000235:genetics
D000418:Albumins; D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D000509:alpha-Fetoproteins; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta