Naslov
Regulation of Survivin Isoform Expression by GLI Proteins in Ovarian Cancer

Autori
Trnski, Diana ; Gregorić, Maja ; Levanat, Sonja ; Ozretić, Petar ; Rinčić, Nikolina ; Majić Vidaković, Tajana ; kalafatić, Držislav ; Maurac, Ivana ; Orešković, Slavko ; Sabol, Maja ; Musani, Vesna

Izvornik
Cells (2073-4409) 8 (2019), 2; 128, 13

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Hedgehog signaling ; GLI proteins ; ovarian cancer ; isoform expression: polymorphisms

Sažetak
Ovarian cancer (OC) is the most lethal female gynecological malignancy, mostly due to diagnosis in late stages when treatment options are limited. Hedgehog-GLI (HH-GLI) signaling pathway is the a major developmental pathway involved in organogenesis and stem cell maintenance, and is activated in OC. One of its targets is survivin (BIRC5), an inhibitor of apoptosis protein (IAP) that plays a role in multiple processes, including proliferation and cell survival. We wanted to investigate the role of different GLI proteins in the regulation of survivin isoform expression (WT, 2α, 2B, 3B and Δex3) in the SKOV-3 OC cell line. We demonstrated that survivin isoforms are downregulated in GLI1 and GLI2 knock-out cell lines, but not in the GLI3 knock-out. Combined tTreatment of GLI1 knock-out cells line with GANT-61 shows an additional inhibitory effect of GANT-61 on several isoforms. Additionally, we examined the expression of survivin isoforms in OC samples and the potential role of BIRC5 polymorphisms in isoform expression. Clinical samples showed the same pattern of survivin isoform expression as in the cell line, and several BIRC5 polymorphisms showed the correlation with isoform expression. Our results showed that survivin isoforms are regulated both by different GLI proteins and BIRC5 polymorphisms in OC.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA