title: Overexpression of KCNJ3 gene splice variants affects vital parameters of the malignant breast cancer cell line MCF-7 in an opposing manner.
abstract: 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.
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
authors: S
authors: S
authors: Rezania
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
authors: S
authors: S
authors: Kammerer
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
authors: C
authors: C
authors: Li
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.|Present address: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: B
authors: B
authors: Steinecker-Frohnwieser
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
authors: A
authors: A
authors: Gorischek
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
authors: T T J
authors: TT
authors: DeVaney
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.|Present address: Institute of Human Genetics, Medical University of Graz, Graz, Austria.
authors: S
authors: S
authors: Verheyen
authors: Institute of Pathophysiology and Immunology, SFL Chicken CAM Laboratory, Medical University of Graz, Graz, Austria.
authors: C A
authors: CA
authors: Passegger
authors: Institute of Pathophysiology and Immunology, SFL Chicken CAM Laboratory, Medical University of Graz, Graz, Austria.
authors: N Ghaffari
authors: NG
authors: Tabrizi-Wizsy
authors: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
authors: H
authors: H
authors: Hackl
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria.
authors: D
authors: D
authors: Platzer
authors: Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.
authors: A H
authors: AH
authors: Zarnani
authors: Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.
authors: E
authors: E
authors: Malle
authors: Institute of Pathology, Medical University of Graz, Graz, Austria.
authors: S W
authors: SW
authors: Jahn
authors: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
authors: T
authors: T
authors: Bauernhofer
authors: Institute of Biophysics, Molecular Physiology Group, Medical University of Graz, Harrachgasse 21/4, Graz, Austria. W.Schreibmayer@gmx.at.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria. W.Schreibmayer@gmx.at.
authors: W
authors: W
authors: Schreibmayer
mesh_terms: D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D049109:Cell Proliferation; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D015854:Up-Regulation
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C497066:KCNJ3 protein, human
keywords: Breast cancer; GIRK1; KCNJ3; MCF-7; Splice variant