RGD Reference Report - Role of estrogen receptor alpha transcriptional coregulators in tamoxifen resistance in breast cancer. - Rat Genome Database

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Role of estrogen receptor alpha transcriptional coregulators in tamoxifen resistance in breast cancer.

Authors: Girault, I  Bieche, I  Lidereau, R 
Citation: Girault I, etal., Maturitas. 2006 Jul 20;54(4):342-51. Epub 2006 Jul 5.
RGD ID: 5130718
Pubmed: PMID:16822624   (View Abstract at PubMed)
DOI: DOI:10.1016/j.maturitas.2006.06.003   (Journal Full-text)

Tamoxifen is the endocrine agent most commonly used at all stages of breast cancer. Estrogen receptor (ER) alpha, which belongs to the superfamily of nuclear receptors, has been used to identify breast cancer patients who are likely to respond to tamoxifen, but resistance nonetheless occurs in 30-50% of treated ER alpha-positive breast cancer patients. The antiproliferative activity of tamoxifen, relying primarily on its ability to compete with estrogen for the ER alpha ligand binding site in breast tumor tissue, hypotheses forwarded to explain treatment failure include: (1) the existence of a second estrogen receptor (ER beta), (2) an imbalance in estrogen biosynthesis and catabolism, (3) altered bioavailability of tamoxifen, (4) altered cellular trafficking of ER alpha, (5) non genomic effects of ER alpha, directly interacting with several signal transduction pathways, and (6) transcriptional dysregulation of ER alpha target genes, which may involve both genomic (ERE alteration) and non genomic alterations. A first non genomic alteration involves the regulation of ER alpha activity by its phosphorylation mediated by growth factors-kinases signaling pathways. A second non genomic alteration, which is the purpose of this review, involves regulatory factors (coregulators) known as coactivators and corepressors, which activate (or repress) the transcription of ER alpha-responsive genes. The regulation process involves both chromatin remodeling and ER alpha interaction with the transcriptional machinery. Thus, dysregulated expression (coactivator overexpression or corepressor underexpression) and/or mutation of these coregulators is thought to impair the action of tamoxifen. Many altered pathways may account for tamoxifen resistance which may be best studied by multigene approaches.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

Objects Annotated

Genes (Rattus norvegicus)
Ncoa3  (nuclear receptor coactivator 3)
Ncor1  (nuclear receptor co-repressor 1)
Ncor2  (nuclear receptor co-repressor 2)
Phb2  (prohibitin 2)

Genes (Mus musculus)
Ncoa3  (nuclear receptor coactivator 3)
Ncor1  (nuclear receptor co-repressor 1)
Ncor2  (nuclear receptor co-repressor 2)
Phb2  (prohibitin 2)

Genes (Homo sapiens)
NCOA3  (nuclear receptor coactivator 3)
NCOR1  (nuclear receptor corepressor 1)
NCOR2  (nuclear receptor corepressor 2)
PHB2  (prohibitin 2)


Additional Information