{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "human", "factors": [{"GSM12744": {"CELL TYPE": "SKR6LR cells, which are SKR6 cells that were treated with increasing lapatinib concentrations (0.2 to 5 \u00ce\u00bcM) for several months to derive a resistant cell population."}}, {"GSM12744": {"CELL TYPE": "SKR6LR cells, which are SKR6 cells that were treated with increasing lapatinib concentrations (0.2 to 5 \u00ce\u00bcM) for several months to derive a resistant cell population."}}, {"GSM12744": {"CELL TYPE": "SKR6LR cells, which are SKR6 cells that were treated with increasing lapatinib concentrations (0.2 to 5 \u00ce\u00bcM) for several months to derive a resistant cell population."}}, {"GSM1274408": {"CELL TYPE": "SKR6CA cells, which are SKR6 cells that were retrovirally transduced with constitutively active NF-\u00ce\u00baB relA/p65 (CAp65) and selected with puromycin"}}, {"GSM1274408": {"CELL TYPE": "SKR6CA cells, which are SKR6 cells that were retrovirally transduced with constitutively active NF-\u00ce\u00baB relA/p65 (CAp65) and selected with puromycin"}}, {"GSM1274408": {"CELL TYPE": "SKR6CA cells, which are SKR6 cells that were retrovirally transduced with constitutively active NF-\u00ce\u00baB relA/p65 (CAp65) and selected with puromycin"}}, {"GSM1274405": {"CELL TYPE": "SKR6-Vector cells, which are SKR6 cells that were retrovirally transduced with the pQCXIP empty retroviral vector and selected with puromycin"}}, {"GSM1274405": {"CELL TYPE": "SKR6-Vector cells, which are SKR6 cells that were retrovirally transduced with the pQCXIP empty retroviral vector and selected with puromycin"}}, {"GSM1274405": {"CELL TYPE": "SKR6-Vector cells, which are SKR6 cells that were retrovirally transduced with the pQCXIP empty retroviral vector and selected with puromycin"}}, {"GSM1274402": {"CELL TYPE": "SKBR-3 cell population with elevated HER2 expression"}}, {"GSM1274402": {"CELL TYPE": "SKBR-3 cell population with elevated HER2 expression"}}, {"GSM1274402": {"CELL TYPE": "SKBR-3 cell population with elevated HER2 expression"}}], "id": 2124, "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are...", "geo_gse_id": "E-GEOD-52707", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 12, "tags": ["breast", "breast cancer", "cancer", "cell", "central"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "nuclear-factor-kappa-b-activation-induced-anti-apo", "geo_id_plat": "E-GEOD-52707_A-AFFY-44", "name": "Nuclear factor kappa B activation-induced anti-apoptosis renders HER2 positive cells drug resistant and accelerates tumor growth", "created": "Jul.11, 2014", "summary": "Breast cancers with HER2 overexpression are sensitive to drugs targeting the receptor or its kinase activity. HER2-targeting drugs are initially effective against HER2- positive breast cancer, but resistance inevitably occurs. We previously found that nuclear factor kappa B is hyper-activated in the subset of HER-2 positive breast cancer cells and tissue specimens. In this study, we report that constitutively active NF-\u03baB rendered HER2-positive cancer cells resistant to anti-HER2 drugs, and cells selected for Lapatinib resistance up-regulated NF-\u03baB. In both circumstances, cells were anti-apoptotic and grew rapidly as xenografts. Lapatinib-resistant cells were refractory to HER2 and NF-\u03baB inhibitors alone but were sensitive to their combination, suggesting a novel therapeutic strategy. A subset of NF-\u03baB-responsive genes was overexpressed in HER2-positive and triple-negative breast cancers, and patients with this NF-\u03baB signature had poor clinical outcome. Anti-HER2 drug resistance may be a consequence of NF-\u03baB activation, and selection for resistance results in NF-\u03baB activation, suggesting this transcription factor is central to oncogenesis and drug resistance. Clinically, the combined targeting of HER2 and NF-\u03baB suggests a potential treatment paradigm for patients who relapse after anti-HER2 therapy. Patients with these cancers may be treated by simultaneously suppressing HER2 signaling and NF-\u03baB activation. We used microarrays to detail the gene expression differences underlying the characterictic survival differences between the SKR6, SKR6-Vector, SKR6CA, and SKR6LR cell lines, which are defined as follows: SKR6: A clonal derivative of SKBR3 cells isolated by fluorescence-activated cell sorting (FACS) to enrich for elevated HER2 levels, SKR6CA: SKR6 cells retrovirally transduced with constitutively active NF-\u03baB relA/p65 (CAp65) and selected with puromycin, SKR6 vector: SKR6 cells transduced with the pQCXIP empty retroviral vector and selected with puromycin, and SKR6LR: SKR6 cells treated with increasing lapatinib concentrations (0.2 to 5 \u03bcM) for several months. We sorted SKBR-3 cells by fluorescence-activated cell sorting (FACS) to enriched for  cell population with elevated HER2 expression, which we termed SKR6. The following cell lines were then created from SKR6 cells: SKR6CA: SKR6 cells retrovirally transduced with constitutively active NF-\u03baB relA/p65 (CAp65), SKR6 vector: SKR6 cells transduced with the pQCXIP empty retroviral vector and selected with puromycin, and SKR6LR: SKR6 cells treated with increasing lapatinib concentrations (0.2 to 5 \u03bcM) for several months.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-52707", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-52707/samples/"}