{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "human", "factors": [{"GSM510103 1": {}}, {"GSM510104 1": {}}, {"GSM510105 1": {}}, {"GSM510106 1": {}}, {"GSM510107 1": {}}, {"GSM510108 1": {}}, {"GSM510109 1": {}}, {"GSM510110 1": {}}], "id": 3582, "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "Endocrine therapies targeting the proliferative effect of 17\u03b2-estradiol (17\u03b2E2) through estrogen receptor \u03b1 (ER\u03b1) are the most effective...", "geo_gse_id": "E-GEOD-20361", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 0, "sample_count": 8, "tags": ["breast", "breast cancer", "cancer", "cell", "estrogen", "line"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "dynamic-changes-during-adaptation-to-estrogen-depr", "geo_id_plat": "E-GEOD-20361_A-AFFY-44", "name": "Dynamic changes during adaptation to estrogen deprivation in MCF7 cell line", "created": "Sep.15, 2014", "summary": "Endocrine therapies targeting the proliferative effect of 17\u03b2-estradiol (17\u03b2E2) through estrogen receptor \u03b1 (ER\u03b1) are the most effective systemic treatment of ER\u03b1-positive breast cancer. However, most breast tumors initially responsive to these therapies develop resistance through a molecular mechanism that is not yet fully understood. The long-term estrogen-deprived (LTED) MCF7 cell model has been proposed to recapitulate acquired resistance to aromatase inhibitors (AIs) in postmenopausal women. To elucidate this resistance, genomic, transcriptomic and molecular data were integrated into the time course of MCF7-LTED adaptation. Dynamic and widespread genomic changes were observed, including amplification of the ESR1 locus consequently linked to an increase in ER\u03b1. Dynamic transcriptomic profiles were also observed that correlated significantly with genomic changes and were influenced by transcription factors known to be involved in acquired resistance or cell proliferation (e.g. IRF1 and E2F1, respectively) but, notably, not by canonical ER\u03b1 transcriptional function. Consistently, at the molecular level, activation of growth factor signaling pathways by EGFR/ERBB/AKT and a switch from phospho-Ser118 (pS118)- to pS167-ER\u03b1 were observed during MCF7-LTED adaptation. Evaluation of relevant clinical settings identified significant associations between MCF7-LTED and breast tumor transcriptome profiles that characterize ER\u03b1-negative status, early response to letrozole and recurrence after tamoxifen treatment. This study proposes a mechanism for acquired resistance to estrogen deprivation that is coordinated across biological levels and independent of canonical ER\u03b1 function. LTED (long term estrogen deprived) cell line was generated from MCF-7 cells by long-term culture under estrogen deprivated conditions. And RNA samples were obtained after 3, 15, 30, 90, 120, 150 and 180 days.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-20361", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-20361/samples/"}