Study of an antiestrogenic effect of retinoic acid in MCF-7 cells.
We recently developed the cellular model MVLN-15 in which estrogenic action can be detected by bioluminescence. Using this cellular model, we characterized the inhibitory effect of retinoic acid on the estrogen-dependent induction of luciferase transcription. We present evidence that i) the inhibitory effect of retinoic acid is not due to a simple competition between retinoic acid and estradiol for binding to the estrogen receptor, ii) a DNA sequence restricted to an estrogen-responsive element (ERE) was sufficient for the antiestrogenic effect of retinoic acid, and iii) retinoic acid does not act via a cryptic AP-1 binding site associated with this ERE. Therefore, we conclude that the antiestrogenic effect of retinoic acid is due to an inhibition of estrogen receptor activity, for example by altering the amount of estrogen receptor protein bound to the ERE or affecting the transcriptional efficiency of this complex.
Demirpence
E
E
INSERM U 58, Montpellier, France.
Pons
M
M
Balaguer
P
P
Gagne
D
D
D001943:Breast Neoplasms / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D008156:Luciferases; D011960:Receptors, Estrogen / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004967:Estrogens; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014212:Tretinoin; D008156:Luciferases