GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A

Gebhard Schratter; Susanne Scheruebel; Sonja Langthaler; Katja Ester; Brigitte Pelzmann; Nassim Ghaffari-Tabrizi-Wizsy; Simin Rezania; Astrid Gorischek; Dieter Platzer; Klaus Zorn-Pauly; Helmut Ahammer; Andreas Prokesch; Stefanie Stanzer; Trevor T J Devaney; Kurt Schmidt; Stephan W Jahn; Ruth Prassl; Thomas Bauernhofer; Wolfgang Schreibmayer

doi:10.1038/s41598-019-55683-w

GIRK1 triggers multiple cancer-related pathways in the benign mammary epithelial cell line MCF10A

Sci Rep. 2019 Dec 17;9(1):19277. doi: 10.1038/s41598-019-55683-w.

Authors

Gebhard Schratter^{1

2}, Susanne Scheruebel^{1

2}, Sonja Langthaler³, Katja Ester⁴, Brigitte Pelzmann^{1

2}, Nassim Ghaffari-Tabrizi-Wizsy⁵, Simin Rezania^{1

2}, Astrid Gorischek^{1

2}, Dieter Platzer^{1

2}, Klaus Zorn-Pauly^{1

2}, Helmut Ahammer¹, Andreas Prokesch^{1

6

7}, Stefanie Stanzer⁸, Trevor T J Devaney^{1

2}, Kurt Schmidt⁹, Stephan W Jahn¹⁰, Ruth Prassl^{1

2}, Thomas Bauernhofer^{8

2}, Wolfgang Schreibmayer^{11

12}

Affiliations

¹ Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.
² Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria.
³ Institute for Health Care Engineering with European Testing Center of Medical Devices, Graz University of Technology, Graz, Austria.
⁴ Laboratory of Experimental Therapy, Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia.
⁵ Institute of Immunology and Pathophysiology, SFL Chicken CAM Laboratory, Medical University of Graz, Graz, Austria.
⁶ Cell Biology, Histology and Embryology, Medical University of Graz, Graz, Austria.
⁷ BioTechMed-Graz, 8010, Graz, Austria.
⁸ Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁹ Institute of Pharmaceutical Sciences, Karl Franzens University of Graz, Graz, Austria.
¹⁰ Diagnostic & Research Institute of Pathology, Medical University of Graz, Graz, Austria.
¹¹ Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria. W.Schreibmayer@gmx.at.
¹² Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Graz, Austria. W.Schreibmayer@gmx.at.

Abstract

Excessive expression of subunit 1 of GIRK1 in ER⁺ breast tumors is associated with reduced survival times and increased lymph node metastasis in patients. To investigate possible tumor-initiating properties, benign MCF10A and malign MCF7 mammary epithelial cells were engineered to overexpress GIRK1 neoplasia associated vital parameters and resting potentials were measured and compared to controls. The presence of GIRK1 resulted in resting potentials negative to the controls. Upon GIRK1 overexpression, several cellular pathways were regulated towards pro-tumorigenic action as revealed by comparison of transcriptomes of MCF10A^GIRK1 with the control (MCF10A^eGFP). According to transcriptome analysis, cellular migration was promoted while wound healing and extracellular matrix interactions were impaired. Vital parameters in MCF7 cells were affected akin the benign MCF10A lines, but to a lesser extent. Thus, GIRK1 regulated cellular pathways in mammary epithelial cells are likely to contribute to the development and progression of breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics*
Breast Neoplasms / pathology
Carcinogenesis / genetics*
Cell Movement / genetics
Female
G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
Gene Expression Regulation, Neoplastic / genetics
Humans
Lymphatic Metastasis
MCF-7 Cells
Mammary Glands, Human / metabolism
Mammary Glands, Human / pathology
Neoplasms / genetics*
Neoplasms / pathology
Transcriptome / genetics

Substances

G Protein-Coupled Inwardly-Rectifying Potassium Channels