Utjecaj utišavanja integrina alfa-v ili alfa-4 na osjetljivost stanica tumora dojke na vinkristin i paklitaksel

master's thesis

• Title (english): Integrin alfa-v or alfa-4 silencing sensitizes human breast carcinoma cell line MDA-MB-435S to vincristine and paclitaxel but has differential effect on cell migration
• Author: Krešimir Ferenčak
• Mentor: Andreja Ambriović Ristov (mentor)
• Mentor: Inga Marijanović (mentor)
• Committee member: Inga Marijanović (predsjednik povjerenstva)
• Committee member: Andreja Ambriović Ristov (član povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Ana Galov (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2013-09-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Integrini su transmembranski heterodimerni proteini koji posreduju u prihvaćanju stanica za druge stanice i izvanstanični matriks. Osim što sudjeluju u regulaciji proliferacije, migracije, metastaziranja i angiogeneze, reguliraju i osjetljivost stanica na protutumorske lijekove. U ovom radu smo odredili učinak utišavanja podjedinica integrina αv, α4, α3, ß3 i ß5 pomoću integrin specifičnih siRNA u stanicama tumora dojke MDA-MB-435S na osjetljivost na protutumorske lijekove koji se koriste u liječenju tumora dojke. Utišavanjem podjedinica αv, α3, ß3 i ß5 smanjuje se osjetljivost stanica MDA-MB-435S na cisplatinu, dok se ne mijenja osjetljivost na doksorubicin i kamptotecin. Međutim, utišavanje podjedinica αv, α4 i ß5 povećava osjetljivost stanica na vinkristin i paklitaksel. Također je pokazano da se sposobnost migracije stanica smanjuje nakon utišavanja podjedinice integrina αv, a povećava nakon utišavanja α4. Ovi rezultati upućuju da bi transfekcija stanica tumora dojke koje eksprimiraju integrine αv, αv-specifičnom siRNA mogla povećati djelotvornost vinkristina i paklitaksela i smanjiti metastatski potencijal.

Abstract (english)

Integrins are heterodimeric transmembrane proteins that mediate the adhesion of cells to other cells and extracellular matrix. Besides regulation of proliferation, migration, metastasis and angiogenesis, integrins regulate cell sensitivity to antitumor drugs. In this study we determine the effect of integrin subunits αv, α4, α3, ß3 and ß5 silencing using integrin-specific siRNA in MDA-MB-435S breast cancer cells in sensitivity to antitumor drugs used in the treatment of breast cancer. αv, α3, ß3 and ß5 subunit silencing reduces sensitivity of cells to cisplatin, while not changing the sensitivity to doxorubicin and kamptotecin. However, αv, α4 and ß5 silencing increases cell sensitivity to vincristine and paclitaxel. It was also shown that the ability of cell migration reduces after αv silencing, and increases after α4 silencing. These results indicate that transfection of breast cancer cells expressing αv integrins with αv-specific siRNA could increase the effectiveness of vincristine and paclitaxel, and at the same time reduce the metastatic potential.

• Keywords: integrini; utišavanje gena; citostatici; migracija stanica
• Keywords (english): integrins; gene silencing; cytostatics; cell migration
• Language: croatian
• URN:NBN: urn:nbn:hr:217:048074
• 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: 2017-04-27 07:48:15