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Inhibition of Serum and Glucocortıcoıd Inducible Kinase 1 (Sgk1) in Triple Negative Breast Cancer

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Date
2018-07-18
Author
Haznedaroğlu , Elif
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Abstract
Glucocorticoid receptor overexpression leads to poor prognosis in breast cancer, particularly in triple negative phenotype. This poor prognosis has been shown to be due to the activation of SGK1 (serum and glucocorticoid inducible kinase 1). In this study, we analyzed SGK1 levels and sensitivity of a panel of TNBC (triple negative breast cancer) cell lines towards SGK1 inhibitor GSK650394. Among these cell lines, MDA-MB-436 cells, displaying markedly elevated SGK1 and showing high phosphorylation of the SGK1 substrate NDRG1 (N-Myc downstream regulated gene 1), was unresponsive to the SGK1 inhibitor. The other cell lines with varying SGK1 levels (MDA MB 231, HCC1937 and BT549) showed marked decrease of NDGR1 phosphorylation due to kinase activity inhibition. Intriguingly, despite GSK650394 sensitivity in these cells, pharmacological SGK1 inhibition did not decrease GSK3β phosphorylation, exhibiting no effect on GSK3β reactivation. In addition, SGK1 inhibition did not change E-cadherin and vimentin expression showing that epithelial-mesenchymal transition (EMT) phenotype was not suppressed. Accordingly, Slug, Snail and Twist mRNA levels were not affected from SGK1 inhibition. GSK650394 treatment suppressed proliferation in MDA-MB-231 cells and led to a slight decrease in S-phase. The results of this study support the idea that SGK1 inhibition strategies may have therapeutic potential in triple negative breast cancer.
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http://hdl.handle.net/11655/4691
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  • Kanser Enstitüsü Tez Koleksiyonu [62]
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Haznedaroğlu, E., Inhibition of Serum and Glucocorticoid Inducible Kinase 1 (SGK1) in Triple Negative Breast Cancer, Hacettepe University Institute of Health Sciences Tumor Biology and Immunology Doctor of Philosophy Thesis, Ankara, 2018.
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