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master's thesis
Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti
Zagreb: University of Zagreb, School of Medicine, 2019. urn:nbn:hr:105:452204
Mioč, Pavao
University of Zagreb
School of Medicine
Department of Gynecology and Obstetrics

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Mioč, P. (2019). Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti (Master's thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:452204

Mioč, Pavao. "Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti." Master's thesis, University of Zagreb, School of Medicine, 2019. https://urn.nsk.hr/urn:nbn:hr:105:452204

Mioč, Pavao. "Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti." Master's thesis, University of Zagreb, School of Medicine, 2019. https://urn.nsk.hr/urn:nbn:hr:105:452204

Mioč, P. (2019). 'Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti', Master's thesis, University of Zagreb, School of Medicine, accessed 09 November 2024, https://urn.nsk.hr/urn:nbn:hr:105:452204

Mioč P. Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti [Master's thesis]. Zagreb: University of Zagreb, School of Medicine; 2019 [cited 2024 November 09] Available at: https://urn.nsk.hr/urn:nbn:hr:105:452204

P. Mioč, "Uloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti", Master's thesis, University of Zagreb, School of Medicine, Zagreb, 2019. Available at: https://urn.nsk.hr/urn:nbn:hr:105:452204

Metadata
TitleUloga proteina Smoothened u razvoju seroznih karcinoma jajnika visokog i niskog stupnja malignosti
Title (english)The role of Smoothened protein in development of high and low grade serous ovarian carcinoma
AuthorPavao Mioč
MentorRatko Matijević (mentor)
Committee memberGoran Vujić (predsjednik povjerenstva)
Committee memberŽeljko Duić (član povjerenstva)
Committee memberRatko Matijević (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
(Department of Gynecology and Obstetrics)
Zagreb
Defense date and country2019-07-12, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Gynecology and Obstetrics
Abstract
Signalni put Hedgehog (Hh) evolucijski je konzerviran i važan u embrionalnom razvoju. Smatra se da je njegova aberantna aktivacija povezana s patogenezom nekih ljudskih karcinoma, a postoje dokazi kako ima određenu ulogu i u razvoju seroznih karcinoma jajnika. Jedan od važnih aktera ovog signalnog puta je protein Smoothened (SMO), transmembranski koreceptor, koji je nakon završenog embrionalnog razvoja uglavnom inhibiran, pa bi njegova ponovna aktivacija mogla dovesti do nekontroliranog rasta i proliferacije stanica. Budući da su istraživanja u čijem je fokusu uloga SMO proteina u seroznim karcinomima jajnika rijetka, cilj ovog istraživanja bio je odrediti ekspresiju proteina SMO i ispitati DNA metilaciju gena SMO u kohorti seroznih karcinoma jajnika. Imunohistokemijski je analizirano 40 seroznih karcinoma jajnika visokog stupnja malignosti (HGSC), 12 seroznih karcinoma jajnika niskog stupnja malignosti (LGSC), 9 uzoraka zdravog tkiva jajovoda i 20 uzoraka zdravog tkiva jajnika koji su korišteni kao kontrole. Metilacija SMO gena analizirana je u 10 HGSC, 10 LGSC, 10 uzoraka zdravog tkiva jajnika i 9 zdravog tkiva jajovoda koji su bili nasumično odabrani. Nuklearna ekspresija SMO bila je statistički značajno veća u HGSC i LGSC u odnosu na zdravo tkivo jajovoda (p=0.010, p=0.003). Membranska i citoplazmatska te ukupna ekspresija bila je statistički značajno veća u LGSC u odnosu na zdravo tkivo jajnika (p=0<001, p=0.001, p<0.001). Uspoređujući HGSC i LGSC nađena je statistički značajno veća ukupna te membranska i citoplazmatska ekspresija SMO u HGSC (p=0.026, p=0.030). Promotor gena SMO bio je nemetiliran kako u karcinomima tako i u kontrolama. Povećana ekspresija proteina SMO, posebno nuklearna, razlikuje tumorsko tkivo seroznih karcinoma jajnika od zdravih kontrola. Budući da promotor gena SMO nije bio metiliran, smatramo da je ekspresija ovoga gena u tkivu jajnika regulirana drugim epigenetskim mehanizmima poput histonske acetilacije za što su potrebna daljnja istraživanja koja će rasvijetliti klinički značaj ovih otkrića.
Abstract (english)
Aberrant Hedgehog (HH) pathway signaling has been implicated in pathogenesis of several human cancers. Furthermore, recent studies have indicated its active role in serous ovarian carcinomas. Smoothened protein (SMO), a transmembrane co-receptor in HH pathway signal transduction, is normally inhibited in non-dividing cells, thus its disinhibition might be a trigger for uncontrolled cell proliferation and growth. However, very few studies have explored the role of SMO in serous ovarian cancers. The aim of this study was to assess the expression of SMO protein and to explore the Smoothened gene promoter methylation in a cohort of serous ovarian carcinomas. SMO protein expression was immunohistochemically quantified in 40 high-grade serous carcinomas (HGSC), 12 low-grade serous carcinomas (LGSC), 20 normal ovarian and 9 normal fallopian tube samples (controls). SMO gene promoter methylation status was analyzed using methylation-specific polymerase chain reaction (MSP) in randomly selected HGSCs (n=10), LGSCs (n=10), normal fallopian tube (n=9) and normal ovarian (n=10) samples. SMO nuclear expression was significantly higher in HGSCs and LGSCs compared with the fallopian tube samples (p=0.010 and p=0.003, respectively). LGSCs, compared with normal ovarian tissue, exhibited higher total, cytoplasmic/membrane and nuclear expression (p<0.001, p=0.001 and p<0.001, respectively). Comparing HGSCs and LGSCs, significantly higher total and cytoplasmic/membrane expression was found in HGSC (p=0.026 and p=0.030, respectively). SMO gene promoter was unmethylated in both LGSCs and HGSCs as well as in fallopian tube. Our data indicate the lack of SMO gene promoter methylation in LGSC, HGSC as well as in controls whereas a significant overexpression (particularly nuclear) of SMO protein characterized a substantial proportion of serous ovarian carcinomas. Further functional studies should elucidate the clinical relevance of these findings.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:105:452204
Study programmeTitle: Medicine
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2019-11-20 14:52:24