POSITIVE AND NEGATIVE REGULATIONS OF ALBUMIN GENE-EXPRESSION BY RETINOIDS IN HUMAN HEPATOMA-CELL LINES

7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (designated '' acyclic retinoid'') induced upregulation of the albumin gene expressio n at its transcriptional level, whereas all-trans-retinoic acid (RA) i nduced downregulation of the expression in both PLC/PRF/5 and HuH7 hum an hepatoma cell lines. These up-and downregulations of the albumin ge ne expression coordinated with high and low levels of mRNA for hepatoc yte nuclear factor-1 (HNF-1), which is one of the most potent transcri ption factors for the albumin gene, implying that retinoids may regula te albumin gene expression through HNF-1 expression in opposite ways. The PLC/PRF/5 and HuH7 hepatoma cell lines expressed retinoid X recept or-alpha (RXR alpha) mRNA, whose expression was constitutive. Acyclic retinoid and all-trans-RA both induced upregulation of retinoic acid r eceptor-beta (RAR beta), and both suppressed cell proliferation-relate d phenotypic expressions by the alpha-fetoprotein gene and the c-myc o ncogene. 9-cis-RA, whose receptor is known to be RXR alpha, also induc ed upregulation of albumin and HNF-1 expression. These results suggest that acyclic retinoid may act through both RXR alpha and RAR beta, wh ereas all-trans-RA conveys only RAR beta-mediated functions, at least in these two hepatoma cell lines. (C) 1994 Wiley-Liss, Inc.