Evidence map›Paper›PMID 25648997›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

A kinetic model identifies phosphorylated estrogen receptor-α (ERα) as a critical regulator of ERα dynamics in breast cancer.

Dan Tian, Natalia M Solodin, Prashant Rajbhandari, Kelsi Bjorklund, Elaine T Alarid, Pamela K Kreeger

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Dan Tian*Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA.
Natalia M Solodin*Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA.
Prashant Rajbhandari*Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA.
Kelsi Bjorklund*Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA.
Elaine T Alarid*Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA.
Pamela K Kreeger*Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, USA kreeger@wisc.edu.
University of Wisconsin Carbone Cancer Center · USUniversity of Wisconsin–Madison · USWisconsin Division of Public Health · US

Funding

Training in Cancer Biology Training GrantT32CA009135 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SUGDEN, WILLIAM M. · 1985 to 2024
$10.4M
Analysis of how quantitative cellular network variation impacts tumor progressionDP2CA195766 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI KREEGER, PAMELA K · 2014 to 2014
$2.3M
Estrogen Receptor Alpha Proteostasis in Breast CancerR01CA159578 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ALARID, ELAINE T · 2011 to 2015
$1.5M
NCI NIH HHS 1DP2CA195766-01NCI NIH HHS CA-159578NCI NIH HHS DP2 CA195766NCI NIH HHS R01 CA159578NCI NIH HHS T32 CA009135
6 · The paper itself

Abstract

Receptor levels are a key mechanism by which cells regulate their response to stimuli. The levels of estrogen receptor-α (ERα) impact breast cancer cell proliferation and are used to predict prognosis and sensitivity to endocrine therapy. Despite the clinical application of this information, it remains unclear how different cellular processes interact as a system to control ERα levels. To address this question, experimental results from the ERα-positive human breast cancer cell line (MCF-7) treated with 17-β-estradiol or vehicle control were used to develop a mass-action kinetic model of ERα regulation. Model analysis determined that RNA dynamics could be captured through phosphorylated ERα (pERα)-dependent feedback on transcription. Experimental analysis confirmed that pERα-S118 binds to the estrogen receptor-1 (ESR1) promoter, suggesting that pERα can feedback on ESR1 transcription. Protein dynamics required a separate mechanism in which the degradation rate for pERα was 8.3-fold higher than nonphosphorylated ERα. Using a model with both mechanisms, the root mean square error was 0.078. Sensitivity analysis of this combined model determined that while multiple mechanisms regulate ERα levels, pERα-dependent feedback elicited the strongest effect. Combined, our computational and experimental results identify phosphorylation of ERα as a critical decision point that coordinates the cellular circuitry to regulate ERα levels.

Indexed as

Models, TheoreticalBlotting, WesternBreast NeoplasmsChromatin ImmunoprecipitationEstradiolEstrogen Receptor alphaEstrogensFeedback, PhysiologicalFemaleGene Expression Regulation, NeoplasticHumansKineticsPhosphorylationPromoter Regions, GeneticReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionESR1 protein, humanEstradiolEstrogen Receptor alphaEstrogensRNA, Messengerfeedbackmathematical modelingnuclear receptorsystems biology

Identifiers

PMID25648997
PMCPMC4415015
OpenAlexW2022159715

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.