Evidence map›Paper›PMID 24779681›Full record

ArticleMolecular cancer2014

Function of RasGRP3 in the formation and progression of human breast cancer.

Zsuzsanna Nagy, Ilona Kovács, Miklós Török, Dezső Tóth, György Vereb, Krisztina Buzás, István Juhász, Peter M Blumberg, Tamás Bíró, Gabriella Czifra

Open access · goldAbstract read
In one paragraph

Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

17 citing papers in PubMed, 33 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

10 authors at 3 institutions in 2 countries.

Zsuzsanna Nagy
Ilona Kovács
Miklós Török
Dezső Tóth
György Vereb
Krisztina Buzás
István Juhász
Peter M Blumberg
Tamás Bíró
Gabriella CzifraDE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, Nagyerdei krt, 98, PO Box 22, Debrecen H-4032, Hungary. czifrag@gmail.com.
University of Debrecen · HUHUN-REN Szegedi Biológiai Kutatóközpont · HUNational Cancer Institute · US

Funding

Molecular Mechanism of Action of Phorbol EsterZIABC005270 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BLUMBERG, PETER · 2009 to 2018
$18.4M
6 · The paper itself

Abstract

introductionRas guanine nucleotide exchange factors (RasGEFs) mediate the activation of the Ras signaling pathway that is over activated in many human cancers. The RasGRP3, an activator of H-Ras and R-Ras protein exerts oncogenic effects and the overexpression of the protein is observed in numerous malignant cancer types. Here, we investigated the putative alteration of expression and potential function of RasGRP3 in the formation and progression of human breast cancer.

methodsThe RasGRP3 and phosphoRasGRP3 expressions were examined in human invasive ductal adenocarcinoma derived samples and cell lines (BT-474, JIMT-1, MCF7, SK-BR-3, MDA-MB-453, T-47D) both in mRNA (Q-PCR) and protein (Western blot; immunohistochemistry) levels. To explore the biological function of the protein, RasGRP3 knockdown cultures were established. To assess the role of RasGRP3 in the viability of cells, annexin-V/PI staining and MitoProbe™ DilC1 (5) assay were performed. To clarify the function of the protein in cell proliferation and in the development of chemotherapeutic resistance, CyQuant assay was performed. To observe the RasGRP3 function in tumor formation, the Severe combined immunodeficiency (SCID) mouse model was used. To investigate the role of the protein in Ras-related signaling Q-PCR and Western blot experiments were performed.

resultsRasGRP3 expression was elevated in human breast tumor tissue samples as well as in multiple human breast cancer cell lines. Down-regulation of RasGRP3 expression in breast cancer cells decreased cell proliferation, induced apoptosis in MCF7 cells, and sensitized T-47D cells to the action of drugs Tamoxifen and trastuzumab (Herceptin). Gene silencing of RasGRP3 reduced tumor formation in mouse xenografts as well. Inhibition of RasGRP3 expression also reduced Akt, ERK1/2 and estrogen receptor alpha phosphorylation downstream from IGF-I insulin like growth factor-I (IGF-I) or epidermal growth factor (EGF) stimulation confirming the functional role of RasGRP3 in the altered behavior of these cells.

conclusionsTaken together, our results suggest that the Ras activator RasGRP3 may have a role in the pathological behavior of breast cancer cells and may constitute a therapeutic target for human breast cancer.

Indexed as

Gene Expression Regulation, NeoplasticAdenocarcinomaAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsApoptosisBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalEpidermal Growth FactorFemaleGuanine Nucleotide Exchange FactorsHumansInsulin-Like Growth Factor IMiceAntibodies, Monoclonal, HumanizedAntineoplastic AgentsEpidermal Growth FactorGuanine Nucleotide Exchange FactorsInsulin-Like Growth Factor IMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Proto-Oncogene Proteins c-aktRASGRP3 protein, humanras Guanine Nucleotide Exchange FactorsRNA, Small InterferingTamoxifenTrastuzumab

Identifiers

PMID24779681
PMCPMC4113147
OpenAlexW2163892074

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.