Uloga androgena i receptora androgena u metastatskom potencijalu tumora glave i vrata

master's thesis

• Title (english): The role of androgens and androgen receptors in the metastatic potential of head and neck tumors
• Author: Janja Josić
• Mentor: Petar Ozretić (mentor)
• Mentor: Inga Urlić (komentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-02-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Muškarci imaju dva do četiri puta veći rizik od obolijevanja od tumora glave i vrata što može biti
posljedica različitih životnih navika muškaraca i žena ili pak posljedica utjecaja njihovih
različitih hormona. Androgeni nastaju sintezom iz kolesterola te obuhvaćaju sve hormone koji
imaju maskulinizirajuće djelovanje. Androgeni svoje djelovanje ostvaruju vezivanjem na jezgrin
(AR) ili membranske receptore (CACNA1C, OXER1, SLC39A9). Hipoteza ovog istraživanja je
da bi androgeni i receptori androgena mogli imati ulogu u razvoju tumora glave i vrata te da bi se
terapija deplecije kolesterola statinima mogla koristiti u liječenju ovog tipa tumora. Metodom
kvantitativne lančane reakcije polimerazom u stvarnom vremenu odredila sam ekspresijski profil
gena za jezgrin i membranske receptore androgena u uzorcima zdravih sluznica, primarnih
tumora, metastatskih limfnih čvorova te u staničnom modelu metastatskog tumora glave i vrata
(stanična linija Detroit 562). Testovima zacjeljivanja rana i formiranja kolonija provjerila sam
migratornu sposobnost stanica nakon aktivacije receptora androgena dihidrotestosteronom i
nakon deplecije kolesterola simvastatinom. Rezultati su pokazali da bi jedino jezgrin receptor
androgena AR mogao imati ulogu u razvoju i metastaziranju tumora glave i vrata te da terapija
deplecije kolesterola predstavlja potencijal u liječenju ovog tipa tumora.

Abstract (english)

Men are at twofold to fourfold higher risk for developing head and neck cancer, which may be a
result of the different lifestyle habits between men and women or a result of their different
hormones. Androgens are synthesised from cholesterol and they include all hormones that have a
masculinizing effect. Androgens exert their action by binding to nuclear (AR) or membrane
receptors (CACNA1C, OXER1, SLC39A9). The hypothesis of this research is that androgens
and androgen receptors could play a role in the development of head and neck tumors and that
cholesterol depletion therapy (caused by statins) could be used in the treatment of this type of
tumor. By using the quantitative polymerase chain reaction in real time, I determined the gene
expression profile for nuclear and membrane androgen receptors in samples of healthy mucosa,
primary tumors, metastatic lymph nodes and also in a metastatic head and neck tumor cell model
(Detroit 562 cell line). By using wound healing and colony forming assays, I investigated the
migratory ability of cells after the activation of androgen receptors with dihydrotestosterone and
after cholesterol depletion with simvastatin. The results showed that only the nuclear androgen
receptor AR could have a role in the development and metastasis of head and neck tumors and
that cholesterol depletion therapy represents a potential novel therapy for this type of tumor.

• Keywords: tumori glave i vrata; receptori androgena; AR; CACNA1C; OXER1; SLC39A9
• Keywords (english): head and neck tumors; androgen receptors; AR; CACNA1C; OXER1; SLC39A9
• Language: croatian
• URN:NBN: urn:nbn:hr:217:299692
• 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: Embargoed access; Embargo expiration date: 2025-02-28
• Created on: 2023-03-15 13:52:36