STANDARD_NAME	BRACHAT_RESPONSE_TO_METHOTREXATE_DN
SYSTEMATIC_NAME	M1498
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BRACHAT_RESPONSE_TO_METHOTREXATE_DN
NAMESPACE	MOUSE_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes down-regulated in  FL5.12 cells (pro-B lymphocyte) in response to methotrexate [PubChem=4112].
DESCRIPTION_FULL	DNA microarrays are powerful tools for the analysis of gene expression on a genomic scale. The importance of individual regulatory events for the process under study can however not be deduced unequivocally without additional experiments. We devised a strategy to identify central regulators of cancer drug responses by combining the results of microarray experiments with efficient methods for phenotypic testing of candidate genes. We exposed murine FL5.12 pro-B cells to cisplatin, camptothecin, methotrexate or paclitaxel, respectively and analysed the patterns of gene expression with cDNA microarrays. Drug-specific regulatory events as well as intersections between different apoptotic pathways, including previously studied responses to staurosporine and interleukin-3 (IL-3) deprivation, were identified. Genes shared by at least three pathways were chosen for further analysis. Ectopic expression of three such genes, TEAP, GP49B, and Lipin1 was found to have an anti-proliferative effect on pro-B cells. Interestingly, we identified hemoglobin alpha as a strong pro-apoptotic regulator. While hemoglobin-expressing cells were growing normally in the presence of IL-3, they displayed accelerated apoptosis with similar kinetics as Bax overexpressing cells upon IL-3 removal. The pro-apoptotic effect of hemoglobin was suppressed by Bcl-2 and was characterized by enhanced stimulation of caspase activity.
PMID	12447701
GEOID	
AUTHORS	Brachat A,Pierrat B,Xynos A,Brecht K,Simonen M,Brüngger A,Heim J
CONTRIBUTOR	John Newman
CONTRIBUTOR_ORG	University of Washington
EXACT_SOURCE	Table 1 & 2: Methotrexate
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AA024085,AA024088,AA028342,AA048837,AA051654,AA060500,AA108822,AA122891,AA182992,AA185446,AA197519,AA204262,AA212445,AA217366,AA265396,AA276216,AA289992,AA397114,AA414831,AA434709,AA499926,AA518639,AA521758,AI595466,AI892192,W11965,W82313
GENE_SYMBOLS	EMILIN2,OSTF1,BNIP3L,IFITM3,MT1F,MIA2,SLC25A1,GAPDH,FKBP3,SASH3,BCL2,ENO1,STAT5A,PDK3,,GPI,IFITM2,ANXA4,HIGD1A,HIKESHI,PPIA,ALDOA,NDUFV3,CORO7,HMGCS1,ENO3,AK4
FOUNDER_NAMES