Uloga proteina GLI u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti

master's thesis

• Title (english): The role of GLI proteins in development of high and low grade serous ovarian carcinoma
• Author: Matea Slavica
• Mentor: Ljiljana Šerman (mentor)
• Committee member: Ratko Matijević (predsjednik povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2017-07-14, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Cytology, Histology and Embryology

Abstract

GLI proteini su transkripcijski čimbenici koji djeluju kao medijatori Hedgehog signalnog puta. Dosadašnja istraživanja povezuju aberantnu aktivnost tog signalnog puta i disregulaciju GLI proteina s nastankom brojnih karcinoma među kojima su karcinom dojke, rabdomiosarkom, kolorektalni karcinom, karcinom pankreasa i glioblastom. Cilj ovog istraživanja bio je ispitati ekspresiju proteina GLI1 i GLI3 u seroznim karcinomima jajnika visokog i niskog stupnja malignosti metodom indirektne imunohistokemije. Sakupljeni su uzorci karcinoma jajnika visokog i niskog stupnja malignosti kao i uzorci zdravog tkiva jajnika koji su korišteni kao kontrola. Imunohistokemijski rezultati kvantificirani su stereolološkom varijablom volumenske gustoće (Vv, mm0) te su statistički obrađeni. Statistički je značajno jača ekspresija GLI1 i GLI3 u seroznom karcinomu jajnika niskog stupnja malignosti u odnosu na zdravo tkivo jajnika, dok te razlike u seroznom karcinomu jajnika visokog stupnja malignosti u odnosu na zdravo tkivo jajnika nije bilo. Također, dobivena je statistički značajno jača ekspresija GLI1 i GLI3 u seroznom karcinomu jajnika niskog stupnja malignosti u odnosu na serozni karcinom jajnika visokog stupnja malignosti. Gledajući ekspresiju u jezgrama, dobivena je statistički značajno jača ekspresija GLI3 u jezgrama seroznog karcinoma niskog i visokog stupnja malignosti u odnosu na jezgre tkiva zdravog jajnika. Štoviše, rezultati pokazuju statistički značajno jaču ekspresiju GLI3 u odnosu na ekspresiju GLI1 u seroznom karcinomu visokog i niskog stupnja malignosti, tkivu zdravog jajnika te u jezgrama seroznog karcinoma jajnika niskog stupnja malignosti. Rezultati ovog istraživanja ukazuju na važnu ulogu Hedgehog signalnog puta u razvoju seroznih karcinoma jajnika te bi daljnja istraživanja ne samo pomnije objasnila njihovu ulogu u karcinogenezi već i omogućila njihovo korištenje u dijagnostici i terapiji.

Abstract (english)

GLI proteins are transcriptional factors which act as of Hedgehog signal pathaway mediators. Current research link the occurence of many carcinomas with aberrant activity of the Hedgehog signal pathway. Among these are breast cancer, rhabdiomiosarcoma, colorectal cancer, pancreatic cancer and glioblastoma. The goal of this study was to examine the expression of GLI1 and GLI3 proteins in both high and low grade serous ovarian carcinomas using indirect immunohistochemistry. Tissue samples of high and low grade serous ovarian carcinomas were collected as well as samples of healthy ovarian tissue which represented control. The results of immunohistochemistry were quantified using the stereological variable of volumetric densitiy (Vv, mm0) and were statistically analyzed. Results showed a statistcally significant higher expression level of GLI1 and GLI3 in low grade serous carcinoma than in healthy ovarian tissue, while statisticallly significant difference of expression level in high grade serous ovarian carcinoma was in comparison to healthy ovarian tissue was not found. Furthermore, a statistically significant higher expression level of GLI1 and GLI3 in low grade serous ovarian carcinoma than in high grade serous ovarian carcinoma was obtained. Examining the nuclear expression level, a statistically significant higher expression level of GLI3 in the cell nuclei of low and high grade serous ovarian carcinoma than in the cell nuclei of healthy ovarian tissue was found. Moreover, a statistically significant higher expression level of GLI3 in relation to GLI1 expression level in both low and high grade serous ovarian carcinoma , healthy ovarian tissue and cell nuclei low grade serous carcinoma nuclei was reported. Results of this research emphasize the significant role of Hedgehog signal pathway in the development of serous ovarian carcinoma. Moreover, further research could not only more closely clarify the role of GLI proteins in carcinogenesis but also enabled their use in diagnostics and therapy.

• Keywords: Hedgehog signalni put; GLI proteini; serozni karcinom jajnika
• Keywords (english): Hedgehog signal pathaway; GLI proteins; serous ovarian carcinoma
• Language: croatian
• URN:NBN: urn:nbn:hr:105:554333
• 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: 2018-03-16 10:53:23