Uloga transkripcijskih faktora GLI u razvoju kožnog melanoma kod ljudi

master's thesis

• Title (english): The role of the GLI family of transcription factors in human skin melanoma development
• Author: Kristina Sladić
• Mentor: Petar Ozretić (mentor)
• Mentor: Jasmina Rokov Plavec (mentor)
• Committee member: Jasmina Rokov Plavec (predsjednik povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Ines Primožič (član povjerenstva)
• Committee member: Morana Dulić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2019-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Ciljevi ovog diplomskog rada jesu povezati razinu ekspresije transkripcijskih faktora GLI1 i
GLI3 sa stadijem razvoja primarnog melanoma kože kod ljudi te ispitati utjecaj inhibicije ili
aktivacije signalnog puta Hedgehog-GLI na stanični ciklus. Na tkivnim preparatima tumora
imunohistokemijskom metodom ispitana je i potvrđena pojačana ekspresija proteina GLI1 i
GLI3. Pokazano je da je ekspresija oba proteina značajno viša u tumorima stadija T4 u
odnosu na tumore in situ (Tis). Ekspresija proteina GLI1 i GLI3 također je ispitana i
potvrđena u humanim staničnim linijama LM6 i WM793B, kao modeli primarnog melanoma,
te u staničnim linijama A375M i Mel224, modelima metastatskog melanoma.
Imunofluorescencijom je određena lokalizacija proteina GLI1 i GLI3 u citoplazmi i jezgri
stanica navedenih staničnih linija. Dodatno je ispitan utjecaj inhibitora (GANT61) i aktivatora
(SAG) signalnog puta na stanični ciklus spomenutih humanih staničnih linija. Stanične linije
značajno reagiraju na tretman GANT-om, dok SAG nema značajan utjecaja na signalni put.

Abstract (english)

The goals of this diploma thesis are to connect the expression level of transcription factors
GLI1 and GLI3 with the stage of human skin melanoma develeopment and examine the
effects of the Hedgehog-GLI signaling pathway inhibition and activation on the cell cycle.
Immunohistochemical analysis of tumor tissue samples confirmed an increased expression of
GLI1 and GLI3 proteins. It was shown that expression of both proteins was significantly
higher in T4 stage tumors compared with in situ tumors (Tis). Expression of GLI1 and GLI3
proteins was also observed in LM6 and WM793B human primary melanoma cell lines and in
A375M and Mel224, human metastatic melanoma cell lines. Localization of GLI1 and GLI3
proteins within the cytoplasm and cell nucleus of those cell lines was determined by
immunofluorescence. The influence of pathway inhibitor (GANT61) and activator (SAG) on
the cell cycle of those human cell lines was also tested. Cell lines are significantly responsive
to GANT treatment, while SAG had no significant influence on the signaling pathway.

• Keywords: GLI1; GLI3; humani kožni melanom; imunofluorescencija; imunohistokemija; signalni put Hedgehog-GLI; stanični ciklus; TNM klasifikacija
• Keywords (english): cell cycle; GLI1; GLI3; Hedgehog-GLI signaling pathway; human skin melanoma; immunofluorescence; immunohistochemistry; TNM classification
• Language: croatian
• URN:NBN: urn:nbn:hr:217:477525
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-02-26
• Created on: 2019-03-20 14:35:09