Positive and negative regulations of albumin gene expression by retinoids in human hepatoma cell lines

Abstract

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/PKF/5 and HuH7 human hepatoma cell lines. These up and downregulations 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 × receptor‐α (RXRα) mRNA, whose expression was constitutive. Acyclic retinoid and all‐trans‐RA both induced upregulation of retinoic acid receptor‐β (RARβ), and both suppressed cell proliferation‐related phenotypic expressions by the α‐fetoprotein gene and the c‐myc oncogene. 9‐cis‐RA, whose receptor is known to be RXRα, also induced upregulation of albumin and HNF‐1 expression. These results suggest that acyclic retinoid may act through both RXRα and RARβ, whereas all‐trans‐RA conveys only RARβ‐mediated functions, at least in these two hepatoma cell lines.