Evidence map›Paper›PMID 27519272›Full record

ArticleBMC cancer2016

Overexpression of KCNJ3 gene splice variants affects vital parameters of the malignant breast cancer cell line MCF-7 in an opposing manner.

S Rezania, S Kammerer, C Li, B Steinecker-Frohnwieser, A Gorischek, T T J DeVaney, S Verheyen, C A Passegger, N Ghaffari Tabrizi-Wizsy, H Hackl and 6 more

Open access · goldAbstract readComparative Study
In one paragraph

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.5field-weighted citation impact, top 28% 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

13 citing papers in PubMed, 18 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

16 authors at 3 institutions in 2 countries.

S RezaniaInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
S KammererInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
C LiInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
B Steinecker-FrohnwieserInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
A GorischekInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
T T J DeVaneyInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
S VerheyenInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
C A PasseggerInstitute of Pathophysiology and Immunology, SFL Chicken CAM Laboratory, Medical University of Graz, Graz, Austria.
N Ghaffari Tabrizi-WizsyInstitute of Pathophysiology and Immunology, SFL Chicken CAM Laboratory, Medical University of Graz, Graz, Austria.
H HacklDivision of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
D PlatzerInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
A H ZarnaniNanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
E MalleInstitute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
S W JahnInstitute of Pathology, Medical University of Graz, Graz, Austria.
T BauernhoferDivision of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
W SchreibmayerInstitute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria. W.Schreibmayer@gmx.at.
Medical University of Graz · ATAcademic Center for Education, Culture and Research · IRInnsbruck Medical University · AT

Funding

Austrian Science Fund FWF KLI 182Austrian Science Fund FWF P 22974
6 · The paper itself

Abstract

backgroundOverexpression the KCNJ3, a gene that encodes subunit 1 of G-protein activated inwardly rectifying K(+) channel (GIRK1) in the primary tumor has been found to be associated with reduced survival times and increased lymph node metastasis in breast cancer patients.

methodsIn order to survey possible tumorigenic properties of GIRK1 overexpression, a range of malignant mammary epithelial cells, based on the MCF-7 cell line that permanently overexpress different splice variants of the KCNJ3 gene (GIRK1a, GIRK1c, GIRK1d and as a control, eYFP) were produced. Subsequently, selected cardinal neoplasia associated cellular parameters were assessed and compared.

resultsAdhesion to fibronectin coated surface as well as cell proliferation remained unaffected. Other vital parameters intimately linked to malignancy, i.e. wound healing, chemoinvasion, cellular velocities / motilities and angiogenesis were massively affected by GIRK1 overexpression. Overexpression of different GIRK1 splice variants exerted differential actions. While GIRK1a and GIRK1c overexpression reinforced the affected parameters towards malignancy, overexpression of GIRK1d resulted in the opposite. Single channel recording using the patch clamp technique revealed functional GIRK channels in the plasma membrane of MCF-7 cells albeit at very low frequency. DISCUSSION: We conclude that GIRK1d acts as a dominant negative constituent of functional GIRK complexes present in the plasma membrane of MCF-7 cells, while overexpression of GIRK1a and GIRK1c augmented their activity. The core component responsible for the cancerogenic action of GIRK1 is apparently presented by a segment comprising aminoacids 235-402, that is present exclusively in GIRK1a and GIRK1c, but not GIRK1d (positions according to GIRK1a primary structure).

conclusionsThe current study provides insight into the cellular and molecular consequences of KCNJ3 overexpression in breast cancer cells and the mechanism upon clinical outcome in patients suffering from breast cancer.

Indexed as

Alternative SplicingBreast NeoplasmsCell AdhesionCell ProliferationFemaleGene Expression Regulation, NeoplasticG Protein-Coupled Inwardly-Rectifying Potassium ChannelsHumansMCF-7 CellsUp-RegulationG Protein-Coupled Inwardly-Rectifying Potassium ChannelsKCNJ3 protein, humanBreast cancerGIRK1KCNJ3MCF-7Splice variant

Identifiers

PMID27519272
PMCPMC4983040
OpenAlexW2511059866

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.