Utjecaj utišavanja integrina alfavbeta3 i alfavbeta5 na osjetljivost stanica tumora na cisplatinu

master's thesis

• Title (english): Influence of integrin αvβ3 and αvβ5 silencing on sensitivity of tumor cells to cisplatin
• Author: Ana Dekanić
• Mentor: Andreja Ambriović Ristov (mentor)
• Mentor: Inga Marijanović (mentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Andreja Ambriović Ristov (član povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2012-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Integrini su transmembranski proteini sastavljeni od α i β podjedinica koji sudjeluju u interakciji između stanica i izvanstaničnog matriksa. Integrini αvβ3 i αvβ5 su eksprimirani na endotelnim stanicama u angiogenezi i na stanicama mnogih tumora i stoga predstavljaju mete za terapiju. Osim toga, reguliraju osjetljivost stanica na protutumorske lijekove. U stanicama tumora dojke MDA-MB-435S istražili smo utjecaj utišavanja integrina αvβ3 i/ili αvβ5 uz pomoć siRNA specifičnih za β3, β5 i αv podjedinice. Pokazali smo da utišavanje β3 podjedinice snižava ekspresiju αvβ3, a povećava ekspresiju αvβ5 integrina, dok se utišavanjem β5 podjedinice snižava ekspresija integrina αvβ5 i povećava ekspresija αvβ3. Utišavanjem podjedinice αv smanjuje se ekspresija αvβ3 i αvβ5 integrina. Utišavanjem ekspresije αvβ3 i/ili αvβ5 integrina čini stanice manje osjetljivima na cisplatinu. Zaključujemo da bi kombinirani pristup liječenju tumora dojke koji eksprimiraju integrine αvβ3 i/ili αvβ5, αv, β3 ili β5-specifičnom siRNA i cisplatinom djelovao antagonistički.

Abstract (english)

Integrins are transmembrane proteins composed of α and β subunits, which actively participate in the interaction between cells and extracellular matrix. Integrins αvβ3 and αvβ5 are expressed on endothelial cells in angiogenesis and on many tumor cells, therefore they represent targets for tumor therapy. Further more, they regulate cell sensitivity to antitumor agents. In MDA-MB-435S breast cancer cell line we investigated the influence of integrin αvβ3 and/or αvβ5 silencing with siRNA specific for β3, β5 and αv subunits. We showed that silencing of β3 subunit decreases the expression of αvβ3, but increases the expression of αvβ5 integrin, while silencing of β5 subunit decreases the expression of αvβ5 and increases the expression of αvβ3. Silencing of αv subunit causes lowering of expression of both αvβ3 and αvβ5 integrins. Silencing of αvβ3 and/or αvβ5 integrin makes cells to be less sensitive to cisplatin. We conclude that the combined approach for αvβ3 and/or αvβ5 integrin positive breast cancer treatment, with siRNA specific for integrin subunits αv, β3 or β5 and cisplatin would have antagonistic effect.

• Keywords: αvβ3; αvβ5; cisplatina; otpornost; utišavanje gena
• Keywords (english): αvβ3; αvβ5; cisplatin; gene silencing; resistance
• Language: croatian
• URN:NBN: urn:nbn:hr:217:578000
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-04-28 12:40:59