Ekspresija izoformi proteina p53 i p73 u staničnim linijama sarkoma mekih tkiva čovjeka

master's thesis

• Title (english): The expression of p53 and p73 isoforms in human soft tissue sarcoma cell lines
• Author: Ana Borić
• Mentor: Neda Slade (mentor)
• Mentor: Maja Matulić (mentor)
• Committee member: Maja Matulić (predsjednik povjerenstva)
• Committee member: Božena Mitić (član povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2019-09-20, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Sarkomi mekih tkiva su zloćudni tumori mezenhimalnog porijekla. Mehanizam tumorigeneze sarkoma mekih tkiva još uvijek je neobjašnjen. Mutacije u genu TP53 su najčešće genetske promjene u tumorima. Porodica p53 obuhvaća gene TP53, TP63 i TP73 koji reguliraju mnoge vitalne biološke procese, uključujući diferencijaciju stanica, proliferaciju i apoptozu. Svaki gen proizvodi proteinske izoforme kroz više mehanizama - alternativnim prekrajanjem, korištenjem alternativnih promotora te različitih mjesta početka translacije. Za razliku od p53, protein p73 prekomjerno je eksprimiran u različitim tumorima i rijetko mutiran. Cilj ovog diplomskog rada je odrediti gensku ekspresiju izoformi gena TP53 i TP73 te proteina p53 i p73 u staničnim linijama sarkoma mekih tkiva čovjeka. Rezultati su pokazali jaču gensku ekspresiju izoformi p53α i Δ133p53α, dok je analiza proteinske ekspresije pokazala višu razinu p53α i Δ40p53α u staničnim linijama u kojima je TP53 mutiran. U staničnim linijama u kojima TP53 nije bio mutiran detektirala sam slabu ekspresiju izoformi p53α, Δ133p53α i p53β. Izoforme gena TP73 slabo su eksprimirane u svim staničnim linijama, a jedino je protein TAp73α značajno eksprimiran u svim staničnim linijama.

Abstract (english)

Soft tissue sarcomas are malignant tumors of mesenchymal origin. The tumorigenic mechanism of soft tissue sarcoma is still unexplained. Mutations in the TP53 gene are the most common genetic changes in tumors. The p53 family includes the TP53, TP63 and TP73 genes that regulate many vital biological processes including cell differentiation, proliferation, and apoptosis. Each gene produces protein isoforms through multiple mechanisms – alternative splicing, use of alternative promoters and alternative translation initiation sites. Unlike p53, protein p73 is rarely mutated but is overexpressed in various tumors. The aim of this graduate thesis is to determine the expression profile of the TP53 and TP73 genes and p53 and p73 proteins in human soft tissue sarcoma cell lines. The results showed stronger gene expression of p53α and Δ133p53α isoforms, while protein analysis revealed higher levels of p53α and Δ40p53α proteins in cell lines with mutated TP53. In TP53 mutant cell lines, I detected poor expression of isoforms p53α, Δ133p53α and p53β. TP73 gene isoforms were poorly expressed in all cell lines, and only TAp73α protein was significantly expressed in all cell lines.

• Keywords: izoforme p53; izoforme p73; sarkom mekih tkiva
• Keywords (english): p53 isoform; p73 isoform; soft tissue sarcoma
• Language: croatian
• URN:NBN: urn:nbn:hr:217:804377
• 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: Open access; Embargo expiration date: 2021-03-29
• Created on: 2019-10-16 07:53:57