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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAeK8Ri9K5Gq42pqczAzagjOKiu7eVy5uZJpLnNsLzUCY#_4 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAeK8Ri9K5Gq42pqczAzagjOKiu7eVy5uZJpLnNsLzUCY#_3 http://www.w3.org/ns/prov#value In breast cancers, estrogen receptor (ER) levels are highly correlated with response to endocrine therapies. We sought to define mechanisms of estrogen (E) signaling in a solid breast tumor model using gene expression profiling. ER(+) T47D-Y human breast cancer cells were grown as xenografts in ovariectomized nude mice under four conditions: 1) 17beta-estradiol for 8 wk (E); 2) without E for 8 wk (control); 3) E for 7 wk followed by 1 wk of E withdrawal (Ewd); or 4) E for 8 wk plus tamoxifen for the last week. E-regulated genes were defined as those that differed significantly between control and E and/or between E and Ewd or control and Ewd. These protocols generated 188 in vivo E-regulated genes that showed two major patterns of regulation. Approximately 46% returned to basal states after Ewd (class I genes); 53% did not (class II genes). In addition, more than 70% of class II-regulated genes also failed to reverse in response to tamoxifen. These genes may be interesting for the study of hormone-resistance issues. A subset of in vivo E-regulated genes appears on lists of clinical ER discriminator genes. These may be useful therapeutic targets or markers of E activity. Comparison of in vivo E-regulated genes with those regulated in identical cells in vitro after 6 and 24 h of E treatment demonstrate only 11% overlap. 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