Naslov
Survivin isoform expresion in GLI1-3 knock-out ovarian carcinoma cell lines

Autori
Gregorić, Maja ; Trnski, Diana ; Sabol, Maja ; Ozretić, Petar ; Levanat, Sonja ; Rinčić, Nikolina ; Kalafatić, Držislav ; Musani, Vesna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Translating Science of Medicine - Targets and Therapeutics - Fifth Meeting of the Croatian Association for Cancer Research with International Participation : Poster presentations, in Libri oncologici, Vol. 46 No. Supplement / Ozretić, Petar ; Levanat, Sonja - Zagreb : Klinički bolnički centar Sestre milosrdnice, 2018, 65-65

Skup
5th Meeting of the Croatian Association for Cancer Research with International Participation: Translating Science to Medicine "Targets and Therapeutics" (HDIR-5)

Mjesto i datum
Zagreb, Hrvatska, 08.11.2018. - 10.11.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BIRC5 ; survivin ; isoforms ; ovarian cancer ; expression

Sažetak
Ovarian cancer is the eighth most common tumor type in women worldwide, and the most lethal female gynecological malignancy with almost no difference in mortality between developed and developing countries. Because it remains asymptomatic for long time it usually gets diagnosed in late stages when treatment options are limited and overall survival remains poor. Hedgehog-GLI (HH-GLI) signaling pathway is one of the major developmental pathways and is responsible for the formation of various tissues and organs, including ovaries. In the adult organism it is involved in the stem cell maintenance, tissue homeostasis and in the immune response. Survivin is an inhibitor of apoptosis protein (IAP) that plays a role in multiple processes, including proliferation and cell survival. It is widely expressed during development, but rarely expressed in adult tissues. Survivin expression in tumors has been associated with aggressive behavior, resistance to radiation and chemotherapy and poor survival. Survivin has at least 5 different splice variants (wild type, 2alpha, 2B, 3B and deltaEx3). The expression levels of various survivin isoforms have been associated with clinicpathologic characteristics in some cancers. Survivin has been recently shown to be a direct target of HH/GLI signaling pathway and has several binding sites for GLI transcription factors in its promoter region. The aim of this study was to investigate the expression of survivin isoforms in SKOV-3 ovarian carcinoma cell line with GLI1-3 knock-outs (KO) treated with GANT-61 pathway inhibitor. GLI1 and GLI2 KO lines show downregulation of survivin isoforms, while GLI3 KO has no effect on expression of survivin isoforms. GLI1 KO regulates expression of all five analyzed isoforms, while GLI2 affects only 3B and deltaEx3 isoforms. Combined treatment of KO cell lines with GANT-61 shows additional inhibitory effect of GANT-61 on wild type, 2alpha and 2B isoforms, suggesting that these isoforms are regulated by both GLI1 and GLI2. On the other hand, 3B and deltaEx3 isoforms are not additionally downregulated by GANT-61 treatment, suggesting a different regulatory mechanism for these two isoforms.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne tehničke znanosti

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