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Enhanced Orai1 and STIM1 Expression as Well as Store Operated Ca2+ Entry in Therapy Resistant Ovary Carcinoma Cells

Enhanced Orai1 and STIM1 Expression as Well as Store Operated Ca2+ Entry in Therapy Resistant Ovary Carcinoma Cells

Sebastian Schmidt, Guoxing Liu, Guilai Liu, Wenting Yang, Sabina Honisch, Stavros Pantelakos, Christos Stournaras, Arnd Hönig, Florian Lang

Oncotarget. 2014 Jul 15;5(13):4799-810.

PMID: 25015419

Abstract:

Mechanisms underlying therapy resistance of tumor cells include protein kinase Akt. Putative Akt targets include store-operated Ca(2+)-entry (SOCE) accomplished by pore forming ion channel unit Orai1 and its regulator STIM1. We explored whether therapy resistant (A2780cis) differ from therapy sensitive (A2780) ovary carcinoma cells in Akt, Orai1, and STIM1 expression, Ca(2+)-signaling and cell survival following cisplatin (100 µM) treatment. Transcript levels were quantified with RT-PCR, protein abundance with Western blotting, cytosolic Ca(2+)-activity ([Ca(2+)]i) with Fura-2-fluorescence, SOCE from increase of [Ca(2+)]i following Ca(2+)-readdition after Ca(2+)-store depletion, and apoptosis utilizing flow cytometry. Transcript levels of Orai1 and STIM1, protein expression of Orai1, STIM1, and phosphorylated Akt, as well as SOCE were significantly higher in A2780cis than A2780 cells. SOCE was decreased by Akt inhibitor III (SH-6, 10 µM) in A2780cis but not A2780 cells and decreased in both cell lines by Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-ABP, 50 µM). Phosphatidylserine exposure and late apoptosis following cisplatin treatment were significantly lower in A2780cis than A2780 cells, a difference virtually abolished by SH-6 or 2-ABP. In conclusion, Orai1/STIM1 expression and function are increased in therapy resistant ovary carcinoma cells, a property at least in part due to enhanced Akt activity and contributing to therapy resistance in those cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415212	Akt Inhibitor III			Price

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