Uloga transkripcijskog faktora NRF2 u ekspresiji akvaporina 3 i akvaporina 5

master's thesis

• Title (english): The role of NRF2 transcription factor on the expression of aquaporin 3 and aquaporin 5
• Author: Ana Josipa Jerončić
• Mentor: Ana Čipak Gašparović (mentor)
• Mentor: Nada Oršolić (komentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Domagoj Đikić (član povjerenstva)
• Committee member: Dubravka Hranilović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-09-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Akvaporin 3 (AQP3) i akvaporin 5 (AQP5) membranski su kanali čija je uloga transport vode i drugih molekula u i van stanice. Često su prekomjerno eksprimirani u brojnim tumorima, uključujući i tumor dojke. Unošenjem molekula poput H₂O₂ utječu na redoks status unutar stanice, rezultirajući u oksidacijskom stresu i posljedično aktivaciji transkripcijskog fatora NRF2. Aktivirani NRF2 ima citoprotektivnu ulogu u zdravim stanicama, dok kod tumorskih stanica dolazi do njegove prekomjerne aktivacije čime stanice postaju otporne na različite vrste terapija. Cilj ovog rada bio je istražiti utjecaj NRF2 na ekspresiju AQP3 i AQP5. Korištenjem aktivatora NRF2, sulforafana, i inhibitora NRF2, ML385, praćen je učinak NRF2 na ekspresiju AQP3 i AQP5 na staničnim linijama raka dojke (pozitivne na receptore za estrogen i progesteron - MCF7, pozitivne na receptor HER2 - SkBr3 i trostruko negativnu, bez receptora za HER2, estrogen i progesteron - SUM159) te na ne-tumorskoj liniji epitela dojke (MCF10A). Promjene su zapažene samo kod staničnih linija MCF7, gdje dolazi do povećane ekspresije hem oksigenaze-1 nakon tretmana sulforafanom, sugerirajući aktivaciju NRF2. Kod stanica SkBr3, zapažava se porast eskpresije AQP3 nakon tretmana s ML385. Kod ostalih staničnih linija nije bilo značajnih promjena nakon modulacije NRF2.

Abstract (english)

Aquaporin 3 (AQP3) and aquaporin 5 (AQP5) are membrane channels whose role is to facilitate transport of water and other molecules in and out of the cell. They are often overexpressed in numerous cancers, including breast cancer. By transporting molecules like H₂O₂, they affect the redox status in the cell, resulting in oxidative stress and consequently the activation of the transcription factor NRF2. Activated NRF2 has a cytoprotective role in healthy cells, while in tumor cells its excessive activation occurs, which makes the cells resistant to various types of therapy. The aim of this work was to investigate the relation between NRF2 and AQP3 and AQP5 expression. Using the NRF2 activator - sulforaphane and the NRF2 inhibitor - ML385, the effect of NRF2 on the expression of AQP3 and AQP5 was monitored in breast cancer cell lines (positive for estrogen and progesterone receptors - MCF7, positive for HER2 receptor – SkBr3 and triple negative; negative for HER2, estrogen and progesteron receptors - SUM159) and on a non-tumorigenous epithelial breast line (MCF10A). Changes were observed only in MCF7 cell line, where increased expression of hem oxigenase-1 occured after treatment with sulforaphane. In SkBr3 cells, changes were observed in AQP3 expression after treatment with ML385. In other cell lines, there were no significant changes after NRF2 modulation.

• Keywords: rak dojke; akvaporin; AQP3; AQP5; NRF2; oksidacijski stres
• Keywords (english): breast cancer; aquaporin; AQP3; AQP5; NRF2; oxidative stress
• Language: croatian
• URN:NBN: urn:nbn:hr:217:248846
• Project: Number: IP-2020-02-3617; Title: Određivanje uloga akvaporina 3 i 5 u razvoju rezistencije tumora dojke na oksidacijski stres; Title: Elucidating the role of aquaporins 3 and 5 in the development of breast cancer resistance to oxidative stress; Acronym: AquaBCaRe; Leader: Ana Čipak Gašparović; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Research Projects
• Study programme: Title: Experimental Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra eksperimentalne biologije (sveučilišni/a magistar/magistra eksperimentalne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-10-03 08:43:47