Human Gene Set: FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN


Standard name FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN
Systematic name M11250
Brief description Genes down-regulated in MCF-7 cells (breast cancer) by selective estrogen receptor modulators (SERM) 4-hydroxytamoxifen, raloxifene, or ICI 182780 but not by estradiol [PubChem=44959;5035;3478439;5757].
Full description or abstract Selective estrogen receptor modulators (SERMs) such as tamoxifen are effective in the treatment of many estrogen receptor-positive breast cancers and have also proven to be effective in the prevention of breast cancer in women at high risk for the disease. The comparative abilities of tamoxifen versus raloxifene in breast cancer prevention are currently being compared in the Study of Tamoxifen and Raloxifene trial. To better understand the actions of these compounds in breast cancer, we have examined their effects on the expression of approximately 12,000 genes, using Affymetrix GeneChip microarrays, with quantitative PCR verification in many cases, categorizing their actions as agonist, antagonist, or partial agonist/antagonist. Analysis of gene stimulation and inhibition by the SERMs trans-hydroxytamoxifen (TOT) and raloxifene (Ral) or ICI 182,780 (ICI) and by estradiol (E2) in estrogen receptor-containing MCF-7 human breast cancer cells revealed that (a) TOT was the most E2-like of the three compounds, (b) all three compounds either partially or fully antagonized the action of E2 on most genes, with the order of antagonist activity being ICI > Ral > TOT, (c) TOT and Ral, but not ICI, displayed partial agonist/partial antagonist activity on a number of E2-regulated genes, (d) several stimulatory cell cycle-related genes were down-regulated exclusively by ICI, (e) the estrogen-like activity of Ral nearly always overlapped with that of TOT, indicating that Ral has little unique agonist activity different from that of TOT, and (f) some genes were specifically up-regulated by TOT but not Ral, ICI, or E2. Hence, gene expression profiling can discern fundamental differences among SERMs and provides insight into the distinct biologies of TOT, Ral, and ICI in breast cancer.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 14973112   Authors: Frasor J,Stossi F,Danes JM,Komm B,Lyttle CR,Katzenellenbogen BS
Exact source Table 6: down-regulated by SERMs or ICI
Related gene sets (show 3 additional gene sets from the source publication)

(show 3 gene sets from any of these authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform or
identifier namespace		 HUMAN_SEQ_ACCESSION
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 49 genes
Gene families ? Categorize these 49 genes by gene family
Show members (show 51 source identifiers mapped to 49 genes)
Version history  

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