TY - GEN A1 - Rezania, Simin A1 - Kammerer, Sarah A1 - Li, Chouyang A1 - Steinecker-Frohnwieser, Bibiane A1 - Gorischek, Astrid A1 - Devaney, Trevor Thomas Joseph A1 - Verheyen, Sarah A1 - Passegger, Christina A1 - Ghaffari Tabrizi-Wizsy, Nassim A1 - Hackl, Hubert A1 - Platzer, Dieter A1 - Zarnani, A.H. A1 - Malle, Ernst A1 - Jahn, Stephan Wenzel A1 - Bauernhofer, Thomas A1 - Schreibmayer, Wolfgang T1 - Overexpression of KCNJ3 gene splice variants affects vital parameters of the malignant breast cancer cell line MCF-7 in an opposing manner T2 - BMC Cancer N2 - Background 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. Methods 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. 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. DiscussionWe 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). Conclusions 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. Y1 - 2016 U6 - https://doi.org/10.1186/s12885-016-2664-8 SN - 1471-2407 VL - 16 ER - TY - GEN A1 - Li, Chouyang A1 - Rezania, Simin A1 - Kammerer, Sarah A1 - Sokolowski, Armin Andreas A1 - Devaney, Trevor Thomas Joseph A1 - Gorischek, Astrid A1 - Jahn, Stephan Wenzel A1 - Hackl, Hubert A1 - Groschner, Klaus A1 - Windpassinger, Christian A1 - Malle, Ernst A1 - Bauernhofer, Thomas A1 - Schreibmayer, Wolfgang T1 - Piezo1 forms mechanosensitive ion channels in the human MCF-7 breast cancer cell line T2 - Scientific Reports N2 - Mechanical interaction between cells - specifically distortion of tensional homeostasis-emerged as an important aspect of breast cancer genesis and progression. We investigated the biophysical characteristics of mechanosensitive ion channels (MSCs) in the malignant MCF-7 breast cancer cell line. MSCs turned out to be the most abundant ion channel species and could be activated by negative pressure at the outer side of the cell membrane in a saturable manner. Assessing single channel conductance (GΛ) for different monovalent cations revealed an increase in the succession: Li⁺ < Na⁺ < K⁺ ≈Rb⁺ ≈ Cs⁺. Divalent cations permeated also with the order: Ca²⁺ < Ba²⁺. Comparison of biophysical properties enabled us to identify MSCs in MCF-7 as ion channels formed by the Piezo1 protein. Using patch clamp technique no functional MSCs were observed in the benign MCF-10A mammary epithelial cell line. Blocking of MSCs by GsMTx-4 resulted in decreased motility of MCF-7, but not of MCF-10A cells, underscoring a possible role of Piezo1 in invasion and metastatic propagation. The role of Piezo1 in biology and progression of breast cancer is further substantiated by markedly reduced overall survival in patients with increased Piezo1 mRNA levels in the primary tumor. Y1 - 2015 U6 - https://doi.org/10.1038/srep08364 SN - 2045-2322 VL - 5 ER -