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Pregled bibliografske jedinice broj: 896627

Časopis

Autori: Ozretić, Petar; Trnski, Diana; Musani, Vesna; Maurac, Ivana; Kalafatić, Držislav; Orešković, Slavko; Levanat, Sonja; Sabol, Maja
Naslov: Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas
( Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas )
Izvornik: International journal of oncology (1019-6439) 51 (2017), 6; 1869-1877
Vrsta rada: članak
Ključne riječi: ovarian carcinoma ; borderline tumors ; Hedgehog signaling ; cyclopamine ; lithium chloride ; Survivin
( ovarian carcinoma ; borderline tumors ; Hedgehog signaling ; cyclopamine ; lithium chloride ; Survivin )
Sažetak:
Hedgehog signaling pathway has been implicated in the pathology of ovarian cancer, and Survivin (BIRC5) has been suggested as a novel target of this pathway. Here we investigated the role of Hedgehog signaling pathway and Survivin in ovarian carcinoma and borderline tumor samples. We aimed to determine possible ways of pathway modulation on primary ovarian cancer cells and an established cell line. RNA was extracted from fresh tumors and control tissues and gene expression was examined using qRT-PCR. Pathway activity in cell lines was examined after treatment with cyclopamine, SHH protein, GANT-61 or lithium chloride using qRT-PCR, western blot and confocal microscopy. The difference between control tissue, borderline tumors and carcinomas can be seen in GLI1 and SUFU gene expression, which is significantly higher in borderline tumors compared to carcinomas. SUFU also shows lower expression levels in higher FIGO stages relative to lower stages. BIRC5 is expressed in all tumors and in healthy ovarian tissues compared to our control tissue, healthy fallopian tube samples. Primary cells developed from ovarian carcinoma tissue respond to cyclopamine treatment with a short-term decrease in cell proliferation, downregulation of Hedgehog pathway genes, including BIRC5, and changes in protein dynamics. Stimulation with SHH protein results in increased cell migration, while GLI1 transfection or PTCH1 silencing demonstrate pathway upregulation. The pathway activity can be modulated by LiCl at the GSK3β-SUFU-GLI level, suggesting at least partial non-canonical activation. Downregulation of the pathway with GANT-61 has proved to be more effective than cyclopamine. GLI inhibitors may be a superior treatment option in ovarian cancer compared to SMO inhibitors.
Projekt / tema: 098-0982464-2461
Izvorni jezik: eng
Rad je indeksiran u
bazama podataka:
Current Contents Connect (CCC)
MEDLINE
Scopus
SCI-EXP, SSCI i/ili A&HCI
Science Citation Index Expanded (SCI-EXP) (sastavni dio Web of Science Core Collectiona)
Kategorija: Znanstveni
Znanstvena područja:
Temeljne medicinske znanosti
URL Internet adrese: https://doi.org/10.3892/ijo.2017.4156
https://www.spandidos-publications.com/10.3892/ijo.2017.4156
Broj citata:
Altmetric:
DOI: 10.3892/ijo.2017.4156
URL cjelovitog teksta:
Google Scholar: Non-canonical Hedgehog signaling activation in ovarian borderline tumors and ovarian carcinomas
Upisao u CROSBI: Petar Ozretić (Petar.Ozretic@irb.hr), 6. Lis. 2017. u 10:55 sati



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