{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Claudia Baldus"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-GEOD-51258"],"description":["ERG overexpression was conducted in stably transfected K562 cell line with a tet-on inducible plasmid habouring ERG3. Prolonged induction of ERG (8 days) produced spindle cell shape changes whereas non-induced cells retained the round morphology. In oder to determine the genes responsible for inducing cell shape changes, a genome wide transcriptional screen was conducted. Three clones that potently induced ERG overexpression (8 days) with the corresponding non-induced cells were hybridized."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Nucleic Acid Extraction - RNA was purified with Qiagen Rneasy Minikit according to manufacturer's conditions","Sample Treatment - K562 pTRE ERG3 cells were induced with 1µg/ml doxycycline daily for 8 days","Growth Protocol - K562 pTRE ERG3 cells were cultured in 10%RMPI 5%CO2","Hybridization - Following fragmentation, 15ug of cRNA were hybridized for 16hr at 45C on GeneChip Human Genome U133 Plus 2.0. GeneChips were washed and stained in the Affymetrix Fluidics Station 450.","Labeling - Biotinylated cRNA were prepared according to the standard Affymetrix protocol from 100ng total RNA (Expression Analysis Technical Manual, 2001, Affymetrix).","Scaning - GeneChips were scanned using the Affymetrix GeneChip Scanner3000"],"figure_sub":["MIAME Score","Raw Data","Organization","Assays and Data","Processed Data","MAGE-TAB Files","Array Designs"],"data_protocol":["Data Transformation - The data were analyzed with Gene Spring using Affymetrix default analysis settings and global scaling as normalization method. The trimmed mean target intensity of each array was arbitrarily set to 1. ID_REF =  VALUE = normalized signal intensity ABS_CALL ="],"omics_type":["Unknown","Transcriptomics","Genomics","Proteomics"],"pubmed_abstract":["Overexpression of the oncogene ERG (ETS-related gene) is an adverse prognostic factor in acute myeloid and T-cell lymphoblastic leukemia (AML and T-ALL). We hypothesize that ERG overexpression is associated with primary drug resistance thereby influencing the outcome in leukemia. We previously reported a cell-line based model of ERG overexpression which induced a potentially chemo-resistant spindle shape cell type. Herein, we report a specific transcriptional gene signature for the observed spindle shaped morphology. Genes significantly over-expressed after ERG induction strongly resembled adhesive mesenchymal-like genes that included integrins (ITGA10, ITGB5, ITGB3, ITGA2B), CD44, and CD24. Interestingly, the mesenchymal-like signature was accompanied by the repression of DNA chromatin remodeling and DNA repair genes, such as CHEK1, EZH2, SUZ12, and DNMT3a. The ERG-induced mesenchymal-like signature positively correlated with TMPRSS2-ERG prostate tissues and invasive breast cancer mRNA expression datasets reflecting a general ERG-driven pattern of malignancy. Furthermore, inhibitors modulating ERG druggable pathways WNT, PKC, and AKT, and chemotherapeutic agent cytarabine revealed ERG-induced drug resistance. In particular, PKC412 treatment enhanced proliferative rates and promoted spindle shape formation in ERG-induced cells. Nilotinib and dasatinib were effective at abolishing ERG-induced cells. Moreover, ERG overexpression also led to an increase in double strand breaks. This report provides mechanistic clues into ERG-driven drug resistance in the poor prognostic group of high ERG expressers, provides insight to improved drug targeted therapies, and provides novel markers for a mesenchymal-like state in acute leukemia."],"study_type":["transcription profiling by array"],"species":["Homo sapiens"],"pubmed_title":["ERG induces a mesenchymal-like state associated with chemoresistance in leukemia cells"],"pubmed_authors":["Verena Nowak","Claudia Baldus","Liliana Mochmann","Martin Neumann","Mochmann LH, Neumann M, von der Heide EK, Nowak V, Kühl AA, Ortiz-Tanchez J, Bock J, Hofmann WK, Baldus CD","Wolf Hofmann"],"additional_accession":[]},"is_claimable":false,"name":"ERG induced mesenchymal like gene signature","description":"ERG overexpression was conducted in stably transfected K562 cell line with a tet-on inducible plasmid habouring ERG3. Prolonged induction of ERG (8 days) produced spindle cell shape changes whereas non-induced cells retained the round morphology. In oder to determine the genes responsible for inducing cell shape changes, a genome wide transcriptional screen was conducted. Three clones that potently induced ERG overexpression (8 days) with the corresponding non-induced cells were hybridized.","dates":{"release":"2013-10-19T00:00:00Z","modification":"2023-09-03T02:19:28.369Z","creation":"2022-02-07T21:27:02.24Z"},"accession":"E-GEOD-51258","cross_references":{"GEO":["GSE51258"],"pubmed":["24504051"],"EFO":["EFO_0002768"]}}