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Rezania, S.
Influences of G-protein activated inwardly rectifying potassium channel subunit 1 on vital parameters of breast cancer cells
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2016. pp. [OPEN ACCESS]
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Authors Med Uni Graz:
Advisor:
Bauernhofer Thomas
Schreibmayer Wolfgang
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Abstract:
Previous studies have shown that overexpression of mRNA or protein of G protein- activated Inwardly rectifying potassium (K+) channel subunit 1 (Girk1 /Kir3.1 ) are associated with increased lymph node metastasis and poor prognosis in breast cancer. In order to test whether GIRK1 overexpression has impact on tumorigenicity, breast cancer cell line derived from MCF-7 stably overexpressing different KCNJ3 splice variants (GIRK1a, GIRK1c and GIRK1d) were produced. Expression levels were quantified by real time PCR and immunocytochemistry. Selected cardinal neoplasia associated vital parameters such as invasion, adhesion, wound healing, proliferation, motility, velocity and angiogenesis were evaluated. Our finding revealed that, overexpression of GIRK1a and GIRK1c significantly increased the invasion, motility coefficient, velocity and wound healing of the cells while overexpression of GIRK1d resulted quite the contrary. In addition, GIRK1d also affected the angiogenesis and increased the G0/G1 phase of cell cycle. Overexpression played no influence on proliferation ( S phase ) and adhesion to fibronectin-coated surface. To conclude, these results have shown that overexpression of GIRK1a and GIRK1c increased the activity of endogenous GIRK complexes, while GIRK1d acts as a dominant negative parts of functional GIRK channel. According to structure of GIRK channel, exon 2 which consist of amino acids 235-307 is important for the cancerogenic action since this fragment is exist in GIRK1a and GIRK1c but missing in GIRK1d splice variant. These results suggest that expression of GIRK1 and shorter splice variants might be a new prognostic biomarkers as well as putative pharmaceutical target for breast cancer but more studies on the mechanism and signaling of GIRK1 channels are required.

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