Evidence map›Paper›PMID 24475282›Full record

ArticlePloS one2014

Activation of ERα signaling differentially modulates IFN-γ induced HLA-class II expression in breast cancer cells.

Ahmed A Mostafa, Dianne Codner, Kensuke Hirasawa, Yumiko Komatsu, Matthew N Young, Viktor Steimle, Sheila Drover

Open access · goldAbstract readComparative Study
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

44 citing papers in PubMed, 85 citations in OpenAlex.

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  7. Sex as a modifier of genetic risk for type 1 diabetes.Diabetes, obesity & metabolism · 2025
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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

7 authors at 2 institutions in 1 country.

Ahmed A MostafaDivision of BioMedical Sciences, Immunology and Infectious Diseases Research Group, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Dianne CodnerDivision of BioMedical Sciences, Immunology and Infectious Diseases Research Group, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Kensuke HirasawaDivision of BioMedical Sciences, Immunology and Infectious Diseases Research Group, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Yumiko KomatsuDivision of BioMedical Sciences, Immunology and Infectious Diseases Research Group, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Matthew N YoungDivision of BioMedical Sciences, Immunology and Infectious Diseases Research Group, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Viktor SteimleDépartement de Biologie, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Sheila DroverDivision of BioMedical Sciences, Immunology and Infectious Diseases Research Group, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
Memorial University of Newfoundland · CAUniversité de Sherbrooke · CA

Funding

Canadian Institutes of Health Research ROP 82352
6 · The paper itself

Abstract

The coordinate regulation of HLA class II (HLA-II) is controlled by the class II transactivator, CIITA, and is crucial for the development of anti-tumor immunity. HLA-II in breast carcinoma is associated with increased IFN-γ levels, reduced expression of the estrogen receptor (ER) and reduced age at diagnosis. Here, we tested the hypothesis that estradiol (E₂) and ERα signaling contribute to the regulation of IFN-γ inducible HLA-II in breast cancer cells. Using a panel of established ER⁻ and ER⁺ breast cancer cell lines, we showed that E₂ attenuated HLA-DR in two ER⁺ lines (MCF-7 and BT-474), but not in T47D, while it augmented expression in ER⁻ lines, SK-BR-3 and MDA-MB-231. To further study the mechanism(s), we used paired transfectants: ERα⁺ MC2 (MDA-MB-231 c10A transfected with the wild type ERα gene) and ERα⁻ VC5 (MDA-MB-231 c10A transfected with the empty vector), treated or not with E₂ and IFN-γ. HLA-II and CIITA were severely reduced in MC2 compared to VC5 and were further exacerbated by E₂ treatment. Reduced expression occurred at the level of the IFN-γ inducible CIITA promoter IV. The anti-estrogen ICI 182,780 and gene silencing with ESR1 siRNA reversed the E2 inhibitory effects, signifying an antagonistic role for activated ERα on CIITA pIV activity. Moreover, STAT1 signaling, necessary for CIITA pIV activation, and selected STAT1 regulated genes were variably downregulated by E₂ in transfected and endogenous ERα positive breast cancer cells, whereas STAT1 signaling was noticeably augmented in ERα⁻ breast cancer cells. Collectively, these results imply immune escape mechanisms in ERα⁺ breast cancer may be facilitated through an ERα suppressive mechanism on IFN-γ signaling.

Indexed as

Analysis of VarianceBlotting, WesternBreast NeoplasmsCell Line, TumorEstradiolEstrogen Receptor alphaFemaleFlow CytometryHistocompatibility Antigens Class IIHumansInterferon-gammaNuclear ProteinsReal-Time Polymerase Chain ReactionReverse Transcriptase Polymerase Chain ReactionRNA, Small InterferingSignal TransductionEstradiolEstrogen Receptor alphaHistocompatibility Antigens Class IIInterferon-gammaMHC class II transactivator proteinNuclear ProteinsRNA, Small InterferingTrans-Activators

Identifiers

PMID24475282
PMCPMC3903652
OpenAlexW1995494263

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.