Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer

Anbalagan, Muralidharan; Rowan, Brian G.

doi:10.1016/j.mce.2015.01.016

Cited by 155 publications

(120 citation statements)

References 78 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…It has been well established that sustained exposure to E2 increases the risk of breast cancer (21), and inhibition of E2-mediated signaling has been suggested as a key strategy for the treatment of estrogen-dependent breast cancer (22,23). In the present study, it was demonstrated that treatment with E2 significantly enhanced the viability, migration and invasion of ERα-positive breast cancer cells.…”

Section: Discussionsupporting

confidence: 56%

“…In addition, the functions of ERα, including chromatin interaction, co-regulator recruitment and gene expression, are regulated by phosphorylation through various kinase signaling pathways, such as mitogen-activated protein kinase/extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B, which have been found to be associated with breast cancer growth and metastasis (21,38,39). In the present study, it was found that miR-203 negatively mediated the protein expression of ERα via direct binding to the 3'UTR of its mRNA.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

Lin

Wang

Gao

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

Lin

Wang

Gao

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…ERα localizes to the nucleus where it may form a homodimer or a heterodimer with ERβ (25). It has previously been demonstrated that E2 and ERα are essential for sexual development and reproductive function, and are involved in some human cancers such as breast cancer and endometrial cancer (26)(27)(28). In the present study, treatment with E2 promoted the viability and migration of ERα-positive breast cancer MCF7 cells.…”

Section: Discussionsupporting

confidence: 59%

miR-148a Suppresses estrogen-induced viability and migration of breast cancer cells via inhibition of estrogen receptor α expression

Feng

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. MicroRNAs (miRs) play critical roles in the development and malignant progression of human cancers. miR-148a has previously been found to inhibit the migration and invasion of breast cancer cells. However, the underlying mechanism of miR-148a in regulating the viability and migration of estrogen receptor (ER) α-positive breast cancer cells is still unknown. In this study, ERα-positive breast cancer MCF7 cells were treated with estradiol (E2). Data from MTT and wound healing assays showed that E2 treatment promoted the viability and migration of MCF7 cells.

show abstract

“…Unfortunately, resistance to the above-mentioned treatment is frequently observed, with progression to more aggressive phenotypes in which ER␣ phosphorylation renders the receptor in an activated conformation independent of ligand activation (33). Therapeutic treatment that can affect the cellular levels of activated ER␣ therefore needs to be developed.…”

Section: Figmentioning

confidence: 99%

A Molecular Mechanism To Switch the Aryl Hydrocarbon Receptor from a Transcription Factor to an E3 Ubiquitin Ligase

Luecke-Johansson

Gralla

Rundqvist

et al. 2017

Molecular and Cellular Biology

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is known as a mediator of toxic responses. Recently, it was shown that the AhR has dual functions. Besides being a transcription factor, it also possesses an intrinsic E3 ubiquitin ligase function that targets, e.g., the steroid receptors for proteasomal degradation. The aim of this study was to identify the molecular switch that determines whether the AhR acts as a transcription factor or an E3 ubiquitin ligase. To do this, we used the breast cancer cell line MCF7, which expresses a functional estrogen receptor alpha (ER␣) signaling pathway. Our data suggest that aryl hydrocarbon receptor nuclear translocator (ARNT) plays an important role in the modulation of the dual functions of the AhR. ARNT knockdown dramatically impaired the transcriptional activation properties of the ligand-activated AhR but did not affect its E3 ubiquitin ligase function. The availability of ARNT itself is modulated by another basic helix-loop-helix (bHLH)-Per-ARNT-SIM (PAS) protein, the repressor of AhR function (AhRR). MCF7 cells overexpressing the AhRR showed lower ER␣ protein levels, reduced responsiveness to estradiol, and reduced growth rates. Importantly, when these cells were used to produce estrogendependent xenograft tumors in SCID mice, we also observed lower ER␣ protein levels and a reduced tumor mass, implying a tumor-suppressive-like function of the AhR in MCF7 xenograft tumors.KEYWORDS aryl hydrocarbon receptor, molecular switch, E3 ubiquitin ligase, transcription factor, aryl hydrocarbon receptor nuclear translocator, aryl hydrocarbon receptor repressor B asic helix-loop-helix (bHLH)-Per-aryl hydrocarbon receptor (AhR) nuclear translocator (ARNT)-SIM (PAS) proteins function as biological sensors that respond to physiological stimuli and environmental signals to mediate adaptive cellular responses. In general, these proteins form heterodimers that consist of a signal-induced subunit and an unregulated, ubiquitously expressed subunit (1). A member of the family of bHLH-PAS proteins is the AhR. Initially identified by Poland and Knutson (2) as a binding site for planar, nonhalogenated, and halogenated xenobiotics, in particular the highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the AhR was viewed for a long time as a mediator of xenobiotic-induced toxicity and carcinogenesis. However, mouse knockdown studies have revealed a role for the AhR beyond xenobiotic-induced toxicity and carcinogenesis. For example, the AhR has been shown to be involved in fetal liver development (3), immune cell modulation and differentiation (4-6), and gastrointestinal homeostasis (7, 8). The developmental defects observed in AhR Ϫ/Ϫ mice and the strong conservation of the AhR throughout evolution (for a review, see reference 9)

show abstract

Estrogen receptor alpha phosphorylation and its functional impact in human breast cancer

Cited by 155 publications

References 78 publications

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells

miR-148a Suppresses estrogen-induced viability and migration of breast cancer cells via inhibition of estrogen receptor α expression

A Molecular Mechanism To Switch the Aryl Hydrocarbon Receptor from a Transcription Factor to an E3 Ubiquitin Ligase

Contact Info

Product

Resources

About