Uloga ekspresije p16 u karcinomima glave i vrata

master's thesis

• Title (english): Role of p16 expression in head and neck carcinoma
• Author: Domagoj Šimatović
• Mentor: Vesna Musani (mentor)
• Mentor: Domagoj Đikić (sumentor)
• Committee member: Domagoj Đikić (predsjednik povjerenstva)
• Committee member: Sven Jelaska (član povjerenstva)
• Committee member: Tomislav Ivanković (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-02-24, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Protein p16, kodiran genom INK4A, pripada obitelji gena INK4 koja ima ulogu tumor supresora i negativno regulira signalni put pRb-E2F. Genetskim promjenama gena INK4A dolazi do potpune inaktivacije ili do smanjene funkcije proteina p16. Karcinomi glave i vrata su tumori koji nastaju na području usne šupljine, ždrijela, grkljana i žlijezda slinovnica. U 50-70% karcinoma glave i vrata nađena je inaktivacija gena INK4A. U ovom diplomskom radu istraživao sam utjecaj ekspresije proteina p16 u stanicama tumora glave i vrata A253, FaDU i Detroit 562, na ekspresiju ciljnih gena te modulaciju tretmana s kemoterapeuticima. Ustanovio sam da kemoterapeutici induciraju ekspresiju gena INK4A u nekim staničnim linijama te da dodatni tretman s p16 pojačava taj efekt. Prateći ekspresiju ciljnih gena p16 utvrdio sam da se genska i proteinska ekspresija gena BIRC5 (proteina survivin) smanjuje pod utjecajem p16. Genska ekspresija gena BIRC5 se smanjivala nakon tretmanima kemoterapeuticima. Tretman doksorubicinom povećao je gensku ekspresiju E2F1 nekim linijama, dok ju je tretman etopozidom i p16 smanjio. Tretmani kemoterapeuticima i p16 utjecali su na stanični ciklus, uzrokovali oštećenje DNA, te apoptozu i smrt stanica. Kombinirani tretmani s p16 i kemoterapeuticima nisu pokazivali jednoznačne rezultate u staničnim linijama, pa se nije moglo zaključiti ima li p16 ikakav dodatni utjecaj.

Abstract (english)

P16 is a protein coded by the INK4A gene that belongs to INK4 gene family. They have a tumor suppressor role and negatively regulate the pRb-E2F signal pathway. When a genetic mutation appears in INK4A, it leads to inactivation of the protein p16 or its improper function. Head and neck carcinomas can occur in the oral cavity, pharynx, larynx or in the salivary glands. In 50-70% of head and neck cancers the inactivation of INK4A was found. In this graduation thesis I studied the influence of p16 protein expression in head and neck cell lines A253, FaDU and Detroit 562 on the expression of target genes and its effect of the treatment with chemotherapeutic drugs. I found that chemotherapeutics induce expression of INK4A gene in some cell lines and that additional treatment with p16 amplifies that effect. Following the expression of the p16 target genes I found that the protein and gene expression of BIRC5 gene (survivin protein) is lowered under the influence of p16. Gene expression of the BIRC5 gene was lowered with chemotherapeutics treatment. Treatment with doxorubicin increased the E2F1 gene expression in some cell lines, but the treatment with etoposide and p16 lowered E2F1 expression. Treatment with chemotherapeutics and p16 influenced the cell cycle, DNA damage, apoptosis, and cell death. Combined treatment of p16 and chemotherapeutics did not show consistent results in cell lines, so I could not make a conclusion if p16 has any additional influence.

• Keywords: INK4A; tretmani; doksorubicin; etopozid
• Keywords (english): INK4A; treatments; doxorubicin; etoposide
• Language: croatian
• URN:NBN: urn:nbn:hr:217:237604
• Study programme: Title: Ecology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra ekologije i zaštite prirode (magistar/magistra ekologije i zaštite prirode)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-02-24
• Created on: 2021-03-09 07:52:26