[Antiestrogenic effect of retinoic acid in MCF-7 cells]

We recently developed the cellular model MVLN-15 in which an 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 was not due to a simple competition between retinoic acid and estradiol for the estrogen receptor binding site, ii) retinoic acid does not significantly modify the parameters of the estradiol binding to the estrogen receptor, iii) retinoic acid does not act at a post-transcriptional level of the estrogenic action, iv) a DNA sequence restricted to an estrogen responsive element (ERE) was sufficient to observe the antiestrogenic effect of retinoic acid, and v) retinoic acid does not act via a cryptic AP-1 binding site associated with this ERE. We concluded 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.