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Series GSE4006 Query DataSets for GSE4006
Status Public on Aug 10, 2006
Title Estrogen effects on MCF-7 breast cancer cells co-expressing ERa and ERb
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Two subtypes of the estrogen receptor, ERalpha and ERbeta, mediate the actions of estrogens, and the majority of human breast tumors contain both ERalpha and ERbeta. To examine the possible interactions and modulatory effects of ERbeta on ERalpha activity, we have used adenoviral gene delivery to produce human breast cancer (MCF-7) cells expressing ERbeta, along with their endogenous ERalpha. We have examined the effects of ERĪ² expression on genome-wide gene expression by Affymetrix GeneChip microarrays. We find that ERbeta modulated estrogen gene expression on nearly 24% of E2-stimulated genes but only 8% of E2-inhibited genes. We find that ERbeta modulation is gene-specific, enhancing or counteracting ERalpha regulation for distinct subsets of estrogen target genes. Introduction of ERbeta into ERalpha-containing cells induced up/down-regulation of many estrogen target in the absence of any added ligand. In addition, ERbeta presence elicited the expression of a unique set of genes that were not regulated by ERalpha alone. ERbeta modulated the expression of genes in many functional categories, but the greatest numbers were associated with transcription factor and signal transduction pathways. Regulation of multiple components in the TGF beta, SDF1, and semaphorin pathways, may contribute to the suppression of proliferation observed with ERbeta both in the presence and absence of estrogen. Hence, ERbeta modulates ERalpha gene regulation in diverse ways that may contribute to its growth-inhibiting beneficial effects in breast cancer
Keywords: modulatory effects of ERb on ERa
Overall design MCF-7 cells expressing endogenous ERalpha were infected with adenovirus carrying either estrogen receptor beta (AdERb) or no insert (Ad) at multiplicity of infection (moi) of 5 or 50. Cells were infected with adenovirus for a period of 48hr before treatment with ligand (vehicle control or 10nM 17beta-estradiol) for a additional period of 24hr before harvest.
Contributor(s) Chang EC, Katzenellenbogen BS
Citation(s) 16809442
Submission date Jan 10, 2006
Last update date Aug 10, 2018
Contact name Edmund C Chang
Organization name Kite Pharma
Street address 2225 Colorado Ave
City Santa Monica
State/province California
ZIP/Postal code 90404
Country USA
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (12)
GSM91260 Ad+veh replicate1
GSM91261 Ad+veh replicate2
GSM91262 Ad+E2 replicate1
BioProject PRJNA95225

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