Evidence map›Paper›PMID 24825907›Full record

ArticleThe Journal of biological chemistry2014

Transcriptional regulation of oncogenic protein kinase Cϵ (PKCϵ) by STAT1 and Sp1 proteins.

HongBin Wang, Alvaro Gutierrez-Uzquiza, Rachana Garg, Laura Barrio-Real, Mahlet B Abera, Cynthia Lopez-Haber, Cinthia Rosemblit, Huaisheng Lu, Martin Abba, Marcelo G Kazanietz

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.2field-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

23 citing papers in PubMed, 32 citations in OpenAlex.

  1. Glutathione-Dependent Pathways in Cancer Cells.International journal of molecular sciences · 2024
    Review
  2. Review
  3. Article
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  6. Glutathione S-Transferases in Cancer.Antioxidants (Basel, Switzerland) · 2021
    Review
  7. Observational
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  20. Sp1-mediated transcriptional regulation of MALAT1 plays a critical role in tumor.Journal of cancer research and clinical oncology · 2015
    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

10 authors at 2 institutions in 2 countries.

HongBin WangFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Alvaro Gutierrez-UzquizaFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Rachana GargFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Laura Barrio-RealFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Mahlet B AberaFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Cynthia Lopez-HaberFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Cinthia RosemblitFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Huaisheng LuFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and.
Martin Abbathe Centro de Investigaciones Inmunológicas Básicas y Aplicadas, Universidad Nacional de La Plata, CP1900 La Plata, Argentina.
Marcelo G KazanietzFrom the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and marcelog@upenn.edu.
University of Pennsylvania · USUniversidad Nacional de La Plata · AR

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
Prostate Carcinogensis and PKC SignalingR01CA089202 · NCI · UNIVERSITY OF PENNSYLVANIA · PI KAZANIETZ, MARCELO G. · 2001 to 2015
$4.5M
NCI NIH HHS R01 CA089202NCI NIH HHS R01-CA89202NIEHS NIH HHS P30 ES013508
6 · The paper itself

Abstract

Overexpression of PKCϵ, a kinase associated with tumor aggressiveness and widely implicated in malignant transformation and metastasis, is a hallmark of multiple cancers, including mammary, prostate, and lung cancer. To characterize the mechanisms that control PKCϵ expression and its up-regulation in cancer, we cloned an ∼ 1.6-kb promoter segment of the human PKCϵ gene (PRKCE) that displays elevated transcriptional activity in cancer cells. A comprehensive deletional analysis established two regions rich in Sp1 and STAT1 sites located between -777 and -105 bp (region A) and -921 and -796 bp (region B), respectively, as responsible for the high transcriptional activity observed in cancer cells. A more detailed mutagenesis analysis followed by EMSA and ChIP identified Sp1 sites in positions -668/-659 and -269/-247 as well as STAT1 sites in positions -880/-869 and -793/-782 as the elements responsible for elevated promoter activity in breast cancer cells relative to normal mammary epithelial cells. RNAi silencing of Sp1 and STAT1 in breast cancer cells reduced PKCϵ mRNA and protein expression, as well as PRKCE promoter activity. Moreover, a strong correlation was found between PKCϵ and phospho-Ser-727 (active) STAT1 levels in breast cancer cells. Our results may have significant implications for the development of approaches to target PKCϵ and its effectors in cancer therapeutics.

Indexed as

Gene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticResponse ElementsTranscription, GeneticBreast NeoplasmsCell Line, TumorFemaleHumansNeoplasm ProteinsProtein Kinase C-epsilonRNA, MessengerRNA, NeoplasmSp1 Transcription FactorSTAT1 Transcription FactorNeoplasm ProteinsPRKCE protein, humanProtein Kinase C-epsilonRNA, MessengerRNA, NeoplasmSp1 Transcription FactorSTAT1 protein, humanSTAT1 Transcription FactorBreast CancerDiacylglycerolGene ExpressionProtein KinaseProtein Kinase C (PKCϵ)Signal TransductionSpecificity Protein 1 (Sp1)STAT Transcription FactorTranscription Promoter

Identifiers

PMID24825907
PMCPMC4094091
OpenAlexW2312906792

What Socratic 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 Socratic graph.