Evidence map›Paper›PMID 27881676›Full record

ArticleThe Journal of biological chemistry2017

Cytoplasmic Localization of Proline, Glutamic Acid, Leucine-rich Protein 1 (PELP1) Induces Breast Epithelial Cell Migration through Up-regulation of Inhibitor of κB Kinase ϵ and Inflammatory Cross-talk with Macrophages.

Brian J Girard, Todd P Knutson, Bethanie Kuker, Laura McDowell, Kathryn L Schwertfeger, Julie H Ostrander

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.5field-weighted citation impact, top 31% 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

12 citing papers in PubMed, 17 citations in OpenAlex.

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  12. Cancer Stem Cell Phenotypes in ERMolecular cancer research : MCR · 2018
    Article
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 2 institutions in 1 country.

Brian J GirardFrom the Masonic Cancer Center and.
Todd P KnutsonFrom the Masonic Cancer Center and.
Bethanie KukerFrom the Masonic Cancer Center and.
Laura McDowellFrom the Masonic Cancer Center and.
Kathryn L SchwertfegerFrom the Masonic Cancer Center and.
Julie H OstranderFrom the Masonic Cancer Center and hans1354@umn.edu.
University of Minnesota Medical Center · USUniversity of Minnesota · US

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)KL2TR000113 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$5.4M
Inflammation in Breast Cancer Initiation and PromotionR01CA132827 · NCI · UNIVERSITY OF MINNESOTA · PI SCHWERTFEGER, KATHRYN L · 2011 to 2015
$1.5M
Does Cytoplasmic PELP1 Predict Resistance To Tamoxifen Chemoprevention?K07CA131501 · NCI · UNIVERSITY OF MINNESOTA · PI OSTRANDER, JULIE H · 2010 to 2014
$580k
NCATS NIH HHS KL2 TR000113NCATS NIH HHS UL1 TR000114NCI NIH HHS K07 CA131501NCI NIH HHS R01 CA132827
6 · The paper itself

Abstract

Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1 (PELP1) is observed in ∼40% of women with invasive breast cancer. In mouse models, PELP1 overexpression in the mammary gland leads to premalignant lesions and eventually mammary tumors. In preliminary clinical studies, cytoplasmic localization of PELP1 was seen in 36% of women at high risk of developing breast cancer. Here, we investigated whether cytoplasmic PELP1 signaling promotes breast cancer initiation in models of immortalized human mammary epithelial cells (HMECs). Global gene expression analysis was performed on HMEC lines expressing vector control, PELP1-wt, or mutant PELP1 in which the nuclear localization sequence was altered, resulting in cytoplasmic localization of PELP1 (PELP1-cyto). Global gene expression analysis identified that PELP1-cyto expression in HMECs induced NF-κB signaling pathways. Western blotting analysis of PELP1-cyto HMECs showed up-regulation of inhibitor of κB kinase ϵ (IKKϵ) and increased phosphorylation of the NF-κB subunit RelB. To determine whether secreted factors produced by PELP1-cyto HMECs promote macrophage activation, THP-1 macrophages were treated with HMEC-conditioned medium (CM). PELP1-cyto CM induced changes in THP-1 gene expression as compared with control cell CM. Double conditioned medium (DCM) from the activated THP-1 cells was then applied to HMECs to determine whether paracrine signaling from PELP1-cyto-activated macrophages could in turn promote migration of HMECs. PELP1-cyto DCM induced robust HMEC migration, which was reduced in DCM from PELP1-cyto HMECs expressing IKKϵ shRNA. Our findings suggest that cytoplasmic localization of PELP1 up-regulates pro-tumorigenic IKKϵ and secreted inflammatory signals, which through paracrine macrophage activation regulates the migratory phenotype associated with breast cancer initiation.

Indexed as

Cell MovementAnimalsBreastCo-Repressor ProteinsCytoplasmEpithelial CellsFemaleGene Expression Regulation, NeoplasticHumansI-kappa B KinaseInflammationMacrophagesMiceNF-kappa BPhosphorylationSignal TransductionCo-Repressor ProteinsI-kappa B KinaseNF-kappa BPELP1 protein, humanTranscription Factorsbreast cancercell migrationcell signalinginflammationmacrophageNF-kB transcription factor

Identifiers

PMID27881676
PMCPMC5217692
OpenAlexW2556558516

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.