Uloga gena HOXB13 i njegovih supstrata u progresiji karcinoma jajnika

master's thesis

• Title (english): HOXB13 and its downstream targets in ovarian cancer progression
• Author: Tonći Šuštić
• Mentor: Nada Oršolić (mentor)
• Committee member: Gordana Lacković-Venturin (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2009, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

HOX geni se povezuju s različitim aspektima neoplastične progresije, budući da ektotopsko izražavanje nekih HOX gena promovira staničnu transformaciju in vitro i tumorogenezu in vivo. Pojačano izražavanje gena HOXB13 primijećeno je kod visokog postotka tumora dojke i jajnika te se povezuje s izrazito agresivnim kliničkim tijekom. Početni cilj ovog istraživanja je ispitati utjecaj ektotopskog izražavanja gena HOXB13 u genetički definiranim modelnim staničnim linijama karcinoma jajnika. Western analizama posredno je identificirano nekoliko gena čije je izražavanje u visokoj pozitivnoj ili negativnoj korelaciji s izražavanjem gena HOXB13. Među ovim genima, posebno se istaknuo klasterin, gen čiji se proteinski produkt (CLU) javlja u dvije izoforme. sCLU posjeduje signalnu sekvencu za sekreciju van stanice te mu se pripisuje citoprotektivna uloga, dok je nCLU lokaliziran u citoplazmi, a u slučaju oštećenja stanice odlazi u jezgru gdje obavlja proapoptotsku ulogu. Kao dio projekta identifikacije novih molekularnih meta koje bi bile podložne terapeutskoj intervenciji u karcinomu jajnika, ovaj rad opisuje proces dobivanja dviju novih staničnih linija koje predstavljaju primjere međusobno disjunktnih uloga klasterina. Dobivene modelne linije analizirane su in vitro i in vivo, te je dokazano stabilno ektotopsko izražavanje obiju klasterinskih izoformi.

Abstract (english)

The HOX genes have been implicated in different aspects of the oncogenic process, as ectopic expression of some HOX genes promotes cellular transformation in vitro and tumorigenesis in vivo. The observation that HOXB13 is expressed in a high percentage of breast and ovarian cancer cell lines and tumors, and that the expression of HOXB13 is associated with a more aggressive clinical course, led us to investigate the ectopic expression of HOXB13 in genetically defined ovarian cancer cell lines. We report identification of several putative HOXB13 targets among which clusterin takes the most prominent role. Clusterin is present in two distinct isoforms, as secreted clusterin (sCLU) and as nuclear clusterin (nCLU). While the former is associated with cell survival, the latter is pro-apoptotic. As a part of the project aiming to identify new therapeutic targets for ovarian cancer, here we describe the generation of clusterinoverexpressing cell lines, representing two contradictory functions of clusterin. These cell lines have subsequently been analyzed using both in vitro and in vivo assays. Consequently, stable ectopic expression of both clusterin isoforms has been demonstrated.

• Keywords: karcinom jajnika; mišji model karcinoma jajnika; HOXB13; klasterin
• Keywords (english): ovarian cancer; mouse model of ovarian cancer; HOXB13; clusterin
• Language: croatian
• URN:NBN: urn:nbn:hr:217:118361
• Study programme: Title: Biology; specializations in: Molecular biology; Course: Molecular biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra biologije (magistar/magistra biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-21 12:53:04