Analogies and differences in the modulation of progesterone receptor induction and cell proliferation by estrogens and antiestrogens in MCF-7 human breast cancer cells: study with 24 triphenylacrylonitrile derivatives.
Structure-activity relationships in a homogeneous series of 24 triphenylacrylonitrile derivatives were examined with respect to the stimulation of progesterone receptor induction and cell proliferation in MCF-7 cells. In general, triphenylacrylonitrile derivatives were found to be full or partial agonists for both responses; the partial agonists were also able to antagonize the stimulatory action of estradiol. The agonistic activities of these molecules decreased as the size of the lateral side chain increased, but the side-chains correlated with partial agonism of progesterone receptor induction were bulkier than those correlated with partial agonism of cell proliferation. Agonistic and antagonistic effects on both responses were correlated with affinity for the estrogen receptor. Half maximal effects on the two responses occurred at different concentrations (4-fold) of the compounds. It can be concluded that in MCF-7 cells, triphenylacrylonitrile modulation of progesterone receptor induction and cell proliferation are mediated by the estrogen receptor; the two effects, which occur at different concentrations and with slightly different substituents of the compounds, are differentially modulated.
Bignon
E
E
INSERM U58, Montpellier, France.
Pons
M
M
Gilbert
J
J
Crastes de Paulet
A
A
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D006801:Humans; D010637:Phenolsulfonphthalein / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D013267:Stilbenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004965:Estrogen Antagonists; D004967:Estrogens; D011980:Receptors, Progesterone; D013267:Stilbenes; D010637:Phenolsulfonphthalein; C037749:triphenylethylene