Epigenetske promjene Wnt signalnog puta u tumorima reproduktivnog sustava

master's thesis

• Title (english): Epigenetic changes of the Wnt signaling pathway in tumors of reproductive system
• Author: Hrvojka Janković
• Mentor: Ljiljana Šerman (mentor)
• Committee member: Tamara Nikuševa Martić (predsjednik povjerenstva)
• Committee member: Sanja Dolanski-Babić (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2015-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Medical Microbiology

Abstract

Epigenetika proučava nasljedne promjene u ekspresiji gena koje se događaju bez promjena u redoslijedu baza molekule DNA. Tri su do danas poznata epigenetska mehanizma: metilacija DNA, modifikacija histona i sinteza malih nekodirajućih RNA. Wnt signalni put se sastoji od heterodimernog receptora sastavljenog od dva tipa transmembranskih proteina na koje se vežu pozitivni ili negativni regulatori staničnog rasta. U slučaju vezanja pozitivnih regulatora, dolazi do translokacije β-katenina u jezgru i aktivacije obitelji o β-kateninu ovisnih transkripcijskih faktora dok vezivanje negativnih regulatora priječi ovaj proces. Jedan od negativnih regulatora Wnt signalnog puta je proteinski produkt gena DACT2 koji djeluje kao tumor supresor, stoga je njegova ekspresija smanjena u kolorektalnom karcinomu i karcinomima želuca. U ovom preglednom radu dan je sistemski prikaz epigenetskih promjena glavnih aktera Wnt signalnog puta i njihov utjecaj na razvoj tumora s naglaskom na tumore reproduktivnog sustava. Posebnu važnost imaju lijekovi koji se primjenjuju u terapiji navedenih tumora, a čiji se terapjiski učinak postiže djelovanjem na epigenetske promjene gena koji kodiraju za glavne proteine Wnt signalnog puta. Izoflavoni koji pripadaju razredu biljnih estrogena, a nalazimo ih u mahunarkama, slanutku i namirnicama od soje, djeluju na signalizaciju putem estrogenskih receptora i mogu modificirati epigenom dojke, uterusa, endometrija, prostate i brojnih drugih organa.

Abstract (english)

Epigenetics studies heritable changes in gene expression that are happening without alterations in the underlying DNA sequence. Up to date, there are three known epigenetic mechanisms: DNA methylation, histone modification and synthesis of small non-coding RNA. Wnt signaling pathway comprises from heterodimer receptor composed of transmembrane proteins onto which positive and negative regulators of cellular growth bind. Binding of positive regulators leads to translocation of β-catenin into the nucleus and activation of β-catenin family- depended transcriptional factors, while binding of negative regulators inhibits this process. One of the negative regulators of Wnt signaling pathway is a protein gene product DACT 2. It acts as a tumor suppressor, hence its expression in colorectal cancer and gastric cancer is diminished. This review demonstrates the systemic look on epigenetic changes among the main effectors of the Wnt signaling pathway and their influence on the tumor development, emphasizing the tumors of reproductive system. Drugs applied in the therapy of the aforementioned tumors are of special importance. Their therapeutic effect is accomplished by the influence on epigenetic changes of genes that code for the main proteins of Wnt signaling pathway. Isoflavones that belong to the class of plant derived compounds with estrogenic activity are found in the pulses, chickpeas, and soy products. Beside their action on the signalization via estrogenic receptors they can also modify epigenome of the breast, uterus, endometrium, prostate and various other organs.

• Keywords: Wnt signalni put; epigenetske promjene; tumori reproduktivnog sustava
• Keywords (english): wnt signaling pathway; epigenetic changes; tumors of the reproductive system
• Language: croatian
• URN:NBN: urn:nbn:hr:105:771657
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-04-04 08:44:14