title: Anti-estrogenic effect of unliganded progesterone receptor is estrogen-selective in breast cancer cells MCF-7.
abstract: We have reported that the ectopic expression of progesterone receptor (PR) in MCF-7 cells disrupted the effects of estradiol-17beta (E2), and this anti-estrogenic effect of PR was associated with heightened E2 metabolism and inhibition of estrogen receptor (ER) binding to estrogen response element (ERE). This study determined if the transfected PR was also able to abolish the effect of other estrogens including estrone (E1), estriol (E3) and estradiol-17alpha. The study revealed that the transfected PR in MCF-7 cells abolished the growth-stimulatory effects of E1 and E2, but had minimal effect on the effects of E3 and estradiol-17alpha. This observation is associated with a faster metabolic inactivation of E1 and E2 than that of E3 and estradiol-17alpha. The conditioned media collected after 72h of E3 treatment from PR-transfected MCF-7 cells retained full estrogenic potential whereas E2-treated conditioned media after 72h have lost all of the estrogenic activity. On the other hand, PR was able to inhibit ER-ERE binding induced by all the estrogens. This suggests that the estrogen-selective anti-estrogenic effect of transfected PR was due to the difference in rate of metabolic inactivation of different estrogens in MCF-7 cells. It is plausible that inhibition of ER-ERE interaction by PR resulted in faster estrogen-ER dissociation, and the dissociated E1 and E2 were metabolically inactivated but enzymes for E3 and estradiol-17alpha inactivation were lacking in MCF-7 cells. The findings suggest an interesting mechanism by which the disruption of ER-ERE interaction heightens the inactivation of estrogens in breast cancer cells.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
authors.forename: Ze-Yi
authors.initials: ZY
authors.lastname: Zheng
authors.forename: Valerie C-L
authors.initials: VC
authors.lastname: Lin
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000502:physiology*; D020218:Response Elements; D014162:Transfection
chemical_list: D020847:Estrogen Receptor Modulators; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone