RGD Reference Report - 9-cis-retinoic acid is more effective than all-trans-retinoic acid in upregulating expression of the alpha-fetoprotein gene. - Rat Genome Database

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9-cis-retinoic acid is more effective than all-trans-retinoic acid in upregulating expression of the alpha-fetoprotein gene.

Authors: Wan, Y J  Pan, T  Wang, L  Locker, J  Wu, T C 
Citation: Wan YJ, etal., J Mol Endocrinol. 1995 Feb;14(1):101-8. doi: 10.1677/jme.0.0140101.
RGD ID: 126790586
Pubmed: PMID:7539613   (View Abstract at PubMed)
DOI: DOI:10.1677/jme.0.0140101   (Journal Full-text)

In McA-RH 8994 rat hepatoma cells, all-trans-retinoic acid (t-RA) induces expression of the alpha-fetoprotein (AFP) and albumin genes and results in a phenotype similar to differentiated fetal hepatocytes. The present study elucidated the mechanism involved in AFP gene regulation mediated by retinoic acid. Northern blot analyses demonstrated that 9-cis-retinoic acid (c-RA), a ligand for retinoid x receptors (RXRs), also induced expression of the AFP gene in McA-RH 8994 cells. The induction was time- and dose-dependent. Northern blots and transfection assays using the 7.3 kb full-length regulatory region of the AFP gene demonstrated that c-RA was more effective than t-RA in regulating expression of the AFP gene. At 10(-7) M, c-RA increased AFP mRNA 5-fold and chloramphenicol acetyltransferase (CAT) activity 2.5-fold. In contrast, t-RA at a concentration of 10(-7) M exerted no significant effect; 10(-6) to 10(-5) M t-RA was needed to affect AFP gene expression. These data suggested that activation of RXRs is essential for the regulation of the AFP gene. Co-transfection experiments revealed that over-expression of RXR alpha in McA-RH 8994 cells further enhanced the CAT activity induced by c-RA. In addition, c-RA did not alter the half-life of AFP mRNA. Thus, RXR alpha may play a crucial role in transcriptional regulation of the AFP gene and in controlling hepatocyte phenotype.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AfpRatcellular response to retinoic acid  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Afp  (alpha-fetoprotein)


Additional Information