Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Rezania, S; Kammerer, S; Li, C; Steinecker-Frohnwieser, B; Gorischek, A; DeVaney, TT; Verheyen, S; Passegger, CA; Tabrizi-Wizsy, NG; Hackl, H; Platzer, D; Zarnani, AH; Malle, E; Jahn, SW; Bauernhofer, T; Schreibmayer, W.
Overexpression of KCNJ3 gene splice variants affects vital parameters of the malignant breast cancer cell line MCF-7 in an opposing manner.
BMC Cancer. 2016; 16(1):628-628 Doi: 10.1186/s12885-016-2664-8 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Führende Autor*innen der Med Uni Graz
Rezania Simin
Schreibmayer Wolfgang
Co-Autor*innen der Med Uni Graz
Bauernhofer Thomas
DeVaney Trevor
Ghaffari Tabrizi-Wizsy Nassim
Gorischek Astrid
Jahn Stephan
Kammerer Sarah
Li Chouyang
Malle Ernst
Passegger Christina Angelika
Platzer Dieter
Steinecker-Frohnwieser Bibiane
Verheyen Sarah

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Overexpression 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. In 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. Adhesion 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. 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). The 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.
Find related publications in this database (using NLM MeSH Indexing)
Alternative Splicing -
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cell Adhesion -
Cell Proliferation -
Female -
G Protein-Coupled Inwardly-Rectifying Potassium Channels - genetics
G Protein-Coupled Inwardly-Rectifying Potassium Channels - metabolism
Gene Expression Regulation, Neoplastic -
Humans -
MCF-7 Cells -
Up-Regulation -

Find related publications in this database (Keywords)
Breast cancer
Splice variant
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