Human Gene Set: MASRI_RESISTANCE_TO_TAMOXIFEN_AND_AROMATASE_INHIBITORS_DN


Standard name MASRI_RESISTANCE_TO_TAMOXIFEN_AND_AROMATASE_INHIBITORS_DN
Systematic name M1991
Brief description Genes down-regulated in derivatives of MCF-7aro cells (breast cancer) that developed resistance to tamoxifen [PubChem=5376] or inhibitors of aromatase (CYP19A1) [GeneID=1588].
Full description or abstract Acquired resistance to either tamoxifen or aromatase inhibitors (AI) develops after prolonged treatment in a majority of hormone-responsive breast cancers. In an attempt to further elucidate mechanisms of acquired resistance to AIs, MCF-7aro cells resistant to letrozole (T+LET R), anastrozole (T+ANA R), and exemestane (T+EXE R), as well as long-term estrogen deprived (LTEDaro) and tamoxifen-resistant (T+TAM R) lines were generated. This is the first complete panel of endocrine therapy-resistant cell lines, which were generated as multiple independent biological replicates for unbiased genome-wide analysis using affymetrix microarrays. Although similarities are apparent, microarray results clearly show gene signatures unique to AI-resistance were inherently different from LTEDaro and T+TAM R gene expression profiles. Based on hierarchical clustering, unique estrogen-responsive gene signatures vary depending on cell line, with some genes up-regulated in all lines versus other genes up-regulated only in the AI-resistant lines. Characterization of these resistant lines showed that LTEDaro, T+LET R, and T+ANA R cells contained a constitutively active estrogen receptor (ER)alpha that does not require estrogen for activation. This ligand-independent activation of ER was not observed in the parental cells, as well as T+EXE R and T+TAM R cells. Further characterization of these resistant lines was performed using cell cycle analysis, immunofluorescence experiments to visualize ER subcellular localization, as well as cross-resistance studies to determine second-line inhibitor response. Using this well-defined model system, our studies provide important information regarding differences in resistance mechanisms to AIs, TAM, and LTEDaro, which are critical in overcoming resistance when treating hormone-responsive breast cancers.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18559539   Authors: Masri S,Phung S,Wang X,Wu X,Yuan YC,Wagman L,Chen S
Exact source Table 4S
Related gene sets (show 1 additional gene sets from the source publication)

(show 2593 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform or
identifier namespace		 HUMAN_GENE_SYMBOL
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 20 genes
Gene families ? Categorize these 20 genes by gene family
Show members (show 20 source identifiers mapped to 20 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.