Uloga glikogen-sintaza-kinaze 3 beta u razvoju karcinoma jajnika

master's thesis

• Title (english): Glycogen synthase kinase-3 beta expression in serous ovarian carcinoma
• Author: Mislav Glibo
• Mentor: Alan Šerman (mentor)
• Committee member: Anita Škrtić (predsjednik povjerenstva)
• Committee member: Dinka Pavičić Baldani (član povjerenstva)
• Committee member: Alan Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Gynecology and Obstetrics); Zagreb
• Defense date and country: 2020-07-17, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Gynecology and Obstetrics
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract

Enzim glikogen-sintaza-kinaza 3ß (GSK3ß) uključen je u regulaciju staničnog metabolizma, staničnog ciklusa, apoptoze i brojnih signalnih putova, a u različitim tumorima i različitim okolnostima djeluje kao promotor ili supresor tumorskog rasta, invazivnosti i metastaziranja. Cilj je ovog rada pregledom literature utvrditi ulogu GSK3ß u razvoju, prognozi i terapiji karcinoma jajnika, najletalnijeg među ginekološkim karcinomima od kojeg godišnje u Hrvatskoj oboli oko 400 žena. Funkcija GSK3ß ovisi o fosforilacijskom statusu enzima. Za aktivnost enzima nužna je fosforilacija na tirozinu 216, koju može provesti sama GSK3ß tijekom procesa vlastite translacije ili neke druge kinaze. Protein-kinaza A i protein-kinaza B (Akt) fosforiliraju GSK3ß na serinu 9 i, onemogućujući time vezanje supstrata, inhibiraju aktivnost GSK3ß. Istraživanja koja su se temeljila na proučavanju ekspresije GSK3ß u karcinomima jajnika otkrila su povećanu ekspresiju, dok istraživanja koja su proučavala kinazu Akt zaključuju da je uslijed povećane aktivnosti Akt u stanicama karcinoma jajnika snižena aktivnost GSK3ß. Čini se da GSK3ß suprimira proces epitelno-mezenhimalne tranzicije, koji je preduvjet za invazivnost i metastaziranje, dok su za prognostičku ulogu GSK3ß u istraživanjima oprečni rezultati. U posljednje se vrijeme ispituje i mogućnost ciljanja GSK3ß kao terapijske mete dvama pristupima, i inhibicijom GSK3ß, i njenom reaktivacijom, te su in vitro dobiveni ohrabrujući rezultati, a neki su od takvih lijekova ušli i u klinička istraživanja. Zaključno, za rasvjetljavanje uloge GSK3ß u razvoju karcinoma jajnika potrebna su daljnja istraživanja, a u klinici individualni pristup svakoj pacijentici.

Abstract (english)

Enzyme glycogen-synthase-kinase 3ß (GSK3ß) is involved in the regulation of the cell metabolism, cell cycle, apoptosis and numerous cellular signalling pathways. In various tumours and under various circumstances, the enzyme could act both
as a promoter and as a suppressor of tumour growth, invasion and metastases formation. The aim of this study was to review the literature on the matter and determine the role GSK3ß plays in the formation of ovarian cancer, the most lethal one among gynaecologic malignancies, with which about 400 women in Croatia get diagnosed annually. The function of GSK3ß depends on its phosphorylation status. For the activity of the enzyme the phosphorylation of tyrosine 216 is needed, which can be phosphorylated by GSK3ß itself during its translation or by some other kinases. On the other hand, protein-kinase A and protein-kinase B (Akt) phosphorylate serine 9 and, by disabling the substrate binding, inhibit catalytic activity of GSK3ß. The studies based on expression of GSK3ß in ovarian cancer cells report increased expression, whereas those concerning Akt conclude that GSK3ß is inactivated in cancer cells due to Akt hyperactivity. It seems that GSK3ß suppresses epithelial-mesenchymal transition, which is a pre-condition for cancer invasion and metastasising. The data on prognostic value of GSK3ß are inconsistent. Recently the possibility of therapeutic targeting GSK3ß has been evaluated, by both inhibiting and reactivating it with encouraging results in vitro, and some of the drugs have entered clinical studies. In conclusion, further research is needed to enlighten the role of GSK3ß in ovarian cancer formation.

• Keywords: glikogen-sintaza-kinaza 3ß; karcinom jajnika
• Keywords (english): glycogen-synthase-kinase 3ß; ovarian cancer
• Language: croatian
• URN:NBN: urn:nbn:hr:105:975931
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-19 11:19:33