Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Mar;122(1-2):1-12.
doi: 10.1007/s00412-012-0392-7. Epub 2012 Nov 29.

Cooperating transcription factors mediate the function of estrogen receptor

Elisa Fiorito  1 , Madhumohan R Katika, Antoni Hurtado
Affiliations
Review

Cooperating transcription factors mediate the function of estrogen receptor

Elisa Fiorito et al. Chromosoma. 2013 Mar.

Abstract

Estrogen receptor (ER) is a hormone-regulated transcription factor that controls cell division and differentiation in the ovary, breast, and uterus. The expression of ER is a common feature of the majority of breast cancers, which is used as a therapeutic target. Recent genetic studies have shown that ER binding occurs in regions distant to the promoters of estrogen target genes. These studies have also demonstrated that ER binding is accompanied with the binding of other transcription factors, which regulate the function of ER and response to anti-estrogen therapies. In this review, we explain how these factors influence the interaction of ER to chromatin and their cooperation for ER transcriptional activity. Moreover, we describe how the expression of these factors dictates the response to anti-estrogen therapies. Finally, we discuss how cytoplasmatic signaling pathways may modulate the function of ER and its cooperating transcription factors.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Role of pioneering factors in regulation of ER chromatin interactions. In the absence of pioneering factors, chromatin regions are tightly packed and are not accessible for ER binding. FOXA1, in cooperation with other transcription factors, opens chromatin regions and facilitates ligand–ER binding. PBX1 seems to have a FOXA1-independent effect
Fig. 2
Fig. 2
ER-cooperating factors influence estrogen-mediated transcription. In breast carcinoma cell lines, the complex created by FOXA1, GATA3, and ER regulates estrogen (red bold dot) transcription. These three factors are necessary for the recruitment of the co-activator p300 and RNA polymerase II. Moreover, XBP1 promotes ER transcriptional activity in a ligand-independent manner. RARA, after binding its ligand ATRA (blue bold dot), interacts and cooperates with ER at ER binding sites, where it stabilizes both ER co-activator and co-repressor binding. PITX-1 represses transcription of a subset of ER-regulated genes
Fig. 3
Fig. 3
The balance between AIB-1 and PAX2 governs ER–tamoxifen action. In breast cancer cells, after tamoxifen treatment (in blue, bound to ER), PAX2 and AIB-1 compete for the binding of ER, and this competition determines tamoxifen response. High levels of PAX2 may recruit co-repressors and other factors that promote chromatin compaction, ER-mediated repression, and tamoxifen sensitivity (on the left). On the contrary, high levels of AIB-1 promote chromatin opening, transcription activation, and tamoxifen resistance (on the right)
Fig. 4
Fig. 4
XBP-1(S) has a role in ligand-independent ER activation and anti-estrogen drug resistance. XBP-1(S) overexpression plays a dual role in estrogen independence and anti-estrogen resistance. XBP-1(S) can bind and activate ER in a ligand-independent manner (upper panel) and induces transcription of BCL-2 gene (lower panel), which might have implications in anti-estrogen drug resistance
Fig. 5
Fig. 5
The crosstalk between growth factor signaling pathways and ER-cooperating factors. Receptor tyrosine kinases EGFR, HER2, and IGFR1 activate downstream signaling pathways including PI3K/Akt, MAP kinases, and ERK. These kinases may phosphorylate ER, which can be activated in a ligand-independent manner. HER2 signaling also regulates FOXA1. ER is activated and interacts with other transcription factors to bind chromatin. IGFR-1 represses PAX2 transcription factor by inducing specific phosphorylation
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abe Y, Ijichi N, et al. Forkhead box transcription factor, forkhead box A1, shows negative association with lymph node status in endometrial cancer, and represses cell proliferation and migration of endometrial cancer cells. Cancer Sci. 2012;103(4):806–812. - PMC - PubMed
    1. Ademuyiwa FO, Thorat MA, et al. Expression of forkhead-box protein A1, a marker of luminal A type breast cancer, parallels low oncotype DX 21-gene recurrence scores. Mod Pathol. 2010;23(2):270–275. - PubMed
    1. Albergaria A, Paredes J, et al. Expression of FOXA1 and GATA-3 in breast cancer: the prognostic significance in hormone receptor-negative tumours. Breast Cancer Res. 2009;11(3):R40. - PMC - PubMed
    1. Ali SA, Zaidi SK, et al. Transcriptional corepressor TLE1 functions with Runx2 in epigenetic repression of ribosomal RNA genes. Proc Natl Acad Sci U S A. 2010;107(9):4165–4169. - PMC - PubMed
    1. Anzick SL, Kononen J, et al. AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer. Science. 1997;277(5328):965–968. - PubMed

Publication types

MeSH terms