Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer | Science Advances

+ breast cancers are also positive for PR,nHighlight:In isolation, both hormones activate or inhibit cellular processes in similar directions, although the magnitude of these effects is less for progestin alone than for estrogen alonenHighlight:PR-mediated antagonism of estrogenic phenotypes is well documentednHighlight:joint activation of ER and PR antagonized ER-regulated oncogenic processesnHighlight:The presence and activity of PR significantly affect the prognostic value of ER.nHighlight:The observed loss of PR protein expression in a subset of ER⁺/PR⁺ breast cancers, because of hypermethylation or deletion of the PR gene locus, results in the loss of ER prognostic valuenHighlight:PR is an essential modulator of ER-regulated genes but also that it significantly contributes to the prognostic value of ER in ER⁺/PR⁺ breast cancersnHighlight:PR-regulated genes have independent prognostic value, and the presence of PR correlates with favorable clinicopathological outcomesnHighlight:These findings emphasize the clinical value of assessing both PR and ER expression in breast cancer samplesnHighlight:this study demonstrates that progestin-activated PR redirects ER chromatin binding and functions as a genomic estrogen agonist and as a phenotypic estrogen antagonist in ER⁺/PR⁺ breast cancer cells and human tumorsn]]>