Inhibition of Serum and Glucocorticoid INducible Kinsae 1 (SGK1) in Triple Negative Breast Cancer

Benlioglu E. H. A. Z. N. E. D. A. R. O. G. L. U., DOĞAN A. L.

UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI, cilt.33, sa.1, ss.37-44, 2023 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 1
  • Basım Tarihi: 2023
  • Doi Numarası: 10.4999/uhod.236832
  • Dergi Adı: UHOD-ULUSLARARASI HEMATOLOJI-ONKOLOJI DERGISI
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE
  • Sayfa Sayıları: ss.37-44
  • Anahtar Kelimeler: Triple negative breast neoplasms, Epithelial-mesenchymal transition, PROTEIN-KINASE, ACTIVATION, RECEPTOR, GROWTH, CELLS
  • Ankara Üniversitesi Adresli: Evet

Özet

Glucocorticoid receptor overexpression leads to poor prognosis in breast cancer, particularly in triple-negative phenotype. prognosis has been sho n to be due to the activation of SGK1 (serum and glucocorticoid inducible kinase 1). The aim of this study is to assess SGK1 levels and sensitivity of a panel of TNBC (triple-negative breast cancer) cell lines to ards SGK1 inhibitor GSK650394 and t o assess the effects of inhibition of SGK1 in TNBC cell lines. Among these cell lines, elevated SGK1 and sho ing high phosphorylation of the SGK1 substrate NDRG1 (N sponsive to the SGK1 inhibitor. The other cell lines ith varying SGK1 levels (MDA-MB-231, HCC1937 and BT549) sho ed marked decrease of NDGR1 phosphorylation due to kinase activity inhibition (n= 3, p< 0.05). Intriguingly, despite GSK650394 these cells, pharmacological SGK1 inhibition did not decrease GSK3 beta phosphorylation, exhibiting no effect on GSK3 beta reactivation (n= 3, p> 0.05). In addition, SGK1 inhibition did not change E-transition (EMT) phenotype as not suppressed (n= 3, p> 0.05). Accordingly, Slug, Snail and T ist mRNA levels ere not from SGK1 inhibition (n= 3, p> 0.05). GSK650394 treatment suppressed proliferation in MDA-MB-231 cells and led to a slight decrease in S-phase. The results of this present study supported the hypothesis that SGK1 inhibition strategies could have therapeutic impact in the management of the triple-negative breast cancer.