{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSM842874": {"INTRACELLULAR DOMAIN OF NOTCH1 (ICN1) STATUS": "On", "CELL LINE": "mouse mammary tumor derived cell line 8534", "AGENT": "Untreated"}}, {"GSM842875": {"INTRACELLULAR DOMAIN OF NOTCH1 (ICN1) STATUS": "Off", "CELL LINE": "mouse mammary tumor derived cell line 8534", "AGENT": "doxycycline"}}, {"GSM842876": {"INTRACELLULAR DOMAIN OF NOTCH1 (ICN1) STATUS": "On", "CELL LINE": "mouse mammary tumor derived cell line 8542", "AGENT": "Untreated"}}, {"GSM842877": {"INTRACELLULAR DOMAIN OF NOTCH1 (ICN1) STATUS": "Off", "CELL LINE": "mouse mammary tumor derived cell line 8542", "AGENT": "doxycycline"}}], "id": 6707, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "NOTCH activation has been recently implicated in human basal-like breast cancers associated with a poor prognosis. To address the role of...", "geo_gse_id": "E-GEOD-34146", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 3, "sample_count": 4, "tags": ["adenocarcinomas", "basal", "breast", "cell", "disease", "embryonic stem cell", "genome", "keratin", "left", "mammary tumor", "notch", "stem cell"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "transcriptional-profiling-of-mmtv-ttatop-icn1-tumo", "geo_id_plat": "E-GEOD-34146_A-AFFY-45", "name": "Transcriptional profiling of MMTV-tTA/TOP-ICN1 tumor derived cell lines comparing untreated (ICN1-On) cells to 24-hour doxcycline treated (ICN1-Off) samples", "created": "Nov.12, 2014", "summary": "NOTCH activation has been recently implicated in human basal-like breast cancers associated with a poor prognosis. To address the role of Notch1 in mammary transformation and mammary tumor initiating cell activity, we developed a doxycycline-regulated model of Notch1-mediated mammary transformation. These mice develop mammary adenocarcinomas that express cytokeratin (CK) 8/18 and contain rare cells that also express keratin 14. In vivo limiting dilution analyses reveal that these mammary tumors exhibit functional heterogeneity and harbor a rare (1/2978) mammary tumor initiating cell population. Using this dox-regulated Notch1 mammary tumor model, we demonstrate that Notch1 inhibition results in mammary tumor regression in vivo and prevents disease recurrence in 4 of 6 tumors tested. Consistent with the in vivo data, Notch1 inhibition reduces mammary tumorsphere forming activity in vitro. Using doxycycline-responsive tumor derived cell lines, we also identify the embryonic stem cell transcription factor Nanog as a novel Notch1-regulated gene in mammospheres. These data indicate that Notch1 contributes to mammary tumor initiating activity and raises the possibility that NOTCH therapeutics may have efficacy in human basal-like breast cancers associated with NOTCH activation. Primary mammary tumors were isolated from two different MMTV-tTA/TOP-ICN1 transgenic mice, minced, enzymatically digested and converted to culture.  To identify changes in gene expression in response to ICN1 suppression, tumor-derived cell lines 8534 and 8542 were left untreated (8534-Untreated; 8542-Untreated) or treated with 2ug/ml doxycycline for 24 hours (8534-Dox; 8542-Dox).  Cells were collected by scraping and total RNA was isolated, followed by real-time PCR validation of NOTCH1 target gene modulation.  RNA samples were further hybridized to Affymetrix mouse genome 430A2.0 arrays.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-34146", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-34146/samples/"}