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Dishevelled family proteins in serous ovarian carcinomas: a clinicopathologic and molecular study |
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| Authors: | Valentina Karin-Kujundzic Vedran Kardum Ida Marija Sola Frane Paic Anita Skrtic Faruk Skenderi Alan Serman Tamara Nikuseva-Martic Semir Vranic Ljiljana Serman |
| Affiliation: | 1. Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia Centre of Excellence in Reproductive and Regenerative Medicine, University of Zagreb School of Medicine, Zagreb, Croatia;2. Department of Obstetrics and Gynecology, University Hospital ‘‘Merkur’’, Zagreb, Croatia;3. Department of Obstetrics and Gynecology, University Hospital ‘‘Sestre Milosrdnice’’, Zagreb, Croatia;4. Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia;5. Centre of Excellence in Reproductive and Regenerative Medicine, University of Zagreb School of Medicine, Zagreb, Croatia Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia Department of Pathology, University Hospital ‘‘Merkur’’, Zagreb, Croatia;6. Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina;7. Centre of Excellence in Reproductive and Regenerative Medicine, University of Zagreb School of Medicine, Zagreb, Croatia Department of Gynecology and Obstetrics, School of Medicine, University of Zagreb, Zagreb, Croatia Clinic of Obstetrics and Gynecology, Clinical Hospital “Sveti Duh”, Zagreb, Croatia;8. College of Medicine, QU Health, Qatar University, Doha, Qatar |
| Abstract: | Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non-canonical Wnt signaling that are important for embryonic development. Since Wnt signaling promotes cell proliferation and invasion, its increased activation is associated with cancer development as well. To get deeper insight into the behavior of Dishevelled proteins in cancer, we studied their expression in serous ovarian carcinomas [both low- (LGSC) and high-grade (HGSC)], and HGSC cell lines OVCAR5, OVCAR8, and OVSAHO. DVL protein expression in serous ovarian carcinomas tissues was analyzed using immunohistochemistry, while DVL protein and mRNA expressions in HGSC cell lines were analyzed using Western blot and quantitative real-time PCR. DVL1 protein expression was significantly higher in LGSC compared with normal ovarian tissue, while DVL3 was overexpressed in both LGSC and HGSC. DVL2 and DVL3 protein expression was higher in HGSC cell lines when compared with normal control cell line FNE1, while DVL1, DVL2, and DVL3 mRNA expression was significantly increased only in OVSAHO cell line. Survival analysis revealed no significant impact of DVL proteins on patients’ outcome. Our data show an active involvement of Dishevelled family proteins in serous ovarian carcinomas. Further studies should confirm the clinical relevance of these observations. |
| Keywords: | Ovary serous carcinoma Dishevelled proteins ovarian carcinoma cell lines Wnt signaling pathway |