9-cis-retinoic acid represses estrogen-induced expression of the very low density apolipoprotein II gene.
The chicken very low density apolipoprotein II (apoVLDLII) gene is estrogen-inducible and specifically expressed in liver. We examined the possible involvement of the retinoid X receptor (RXR) and its ligand 9-cis-retinoic acid (9-cis-RA) in the activation of the apoVLDLII promoter. We first concentrated on a potential RXR recognition site, which deviates at only one position from a perfect direct A/GGGTCA repeat spaced by one nucleotide (DR-1) and was earlier identified as a common HNF-4/COUP-TF recognition site. However, band shift analysis revealed that this imperfect DR-1 motif does not interact with RXR alpha-homodimers. In accordance with this observation we found that this regulatory element does not mediate transactivation through RXR alpha in the presence of 9-cis-RA. However, our experiments revealed another, unexpected, effect of 9-cis-RA. Instead of stimulating, 9-cis-RA attenuated estrogen-induced expression of transfected estrogen-responsive VLDL-CAT reporter plasmids. This repression appeared to take place through the main estrogen response element (ERE) of the gene. Importantly, 9-cis-RA also strongly repressed the estrogen-induced expression of the endogenous apoVLDLII gene in cultured chicken hepatoma cells.
Department of Biochemistry, University of Groningen, The Netherlands.
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Kloppenburg
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D000818:Animals; D001053:Apolipoproteins / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D015152:Blotting, Northern; D002645:Chickens; D015342:DNA Probes / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004967:Estrogens / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics / Q000502:physiology; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D001053:Apolipoproteins; D015342:DNA Probes; D004967:Estrogens; D011498:Protein Precursors; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C054949:apolipoprotein II; D014212:Tretinoin