M. Sc. Thesis
Marija Gjorgoska (Author), Petra Golja (Reviewer), Tea Lanišnik-Rižner (Mentor), Petra Golja (Thesis defence commission member), Rok Kostanjšek (Thesis defence commission member), Maša Sinreih (Co-mentor)

Abstract

Endometrial (EC) and ovarian (OC) cancers are generally considered as post-menopausal, hormone-dependent pathologies with increasing incidence and mortality rate. Estrogen intracrine action is regarded vital in the cancer initiation and progression. Estrogens can form locally from androgen and estrogen precursors, through the aromatase and the sulfatase pathway, respectively. Here we intend to elucidate the contribution of the sulfatase pathway to active estrogen formation in model cell lines of EC and OC, by means of liquid chromatography-tandem mass spectrometry (LC-MS/MS). For this purpose we developed a robust LC-MS/MS method with a picomolar sensitivity for the following analytes: estrone (E1), estrone sulfate (E1-S), estradiol (E2), and estradiol sulfate (E2-S). Control and mode l cell lines of EC andOC were incubated with different E1-S concentrations for 8, 24, 48, and 72 hours, and the formed metabolites analyzed by LC-MS/MS. Our data indicate that the sulfatase pathway contributes to the estrogen formation actively, yet differently in EC and OC model cell lines and the respective control lines. More specifically, greater levels of E1and E2 are synthesized in the EC and OC model cell lines comparing to the respective control lines, altogether implyingan active role of estrogen in EC and OC carcinogenesis, acting as pro-proliferative hormones and/or genotoxic agents.

Keywords

endometrial cancer;ovarian cancer;estrogen formation;

Data

Language: English
Year of publishing:
Typology: 2.09 - Master's Thesis
Organization: UL MF - Faculty of Medicine
Publisher: [M. Gjorgoska]
UDC: 618.1
COBISS: 55705859 Link will open in a new window
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Other data

Secondary language: Slovenian
Secondary title: Sinteza estrogenov v celičnih linijah raka endometrija in jajčnikov
Secondary abstract: Rak endometrija (angl. endometrial cancer/EC) in jajčnikov (angl. ovarian cancer/OC) splošno obravnavamo kot hormonsko odvisni patologiji, ki sta značilni za obdobje po menopavzi, z naraščujočo pojavnostjo in smrtnostjo. Intrakrino delovanje estrogenov razumemo kot ključno pri začetku in napredovanju raka. Estrogeni se lahko tvorijo lokalno iz androgenih in estrogenih prekurzorjev, po aromatazni in sulfatazni poti. V tem delu nameravamo razjasniti prispevek sulfatazne poti pri nastanku aktivnih estrogenov v modelnih celičnih linijah EC in OC, s pomočjo tekočinske kromatografije sklopljene z masno spektrometrijo (LC-MS/MS). V ta namen smo razvili robustno LC-MS/MS metodo s pikomolarno občutljivostjo za sledeče analite: estron (E1), estron sulfat (E1-S), estradiol (E2), in estradiol sulfat (E2-S). Kontrolne in modelne celične linije EC in OC smo inkubirali z različnimi koncentracijami E1-S, 8, 24, 48, in 72 ur in nastale metabolite analizirali z LC-MS/MS. Naši podatki kažejo, da sulfatazna pot aktivno prispeva k nastanku estrogenov, vendar različno pri EC in OC modelnih celičnih linijah v primerjavi z ustreznimi kontrolnimi celičnimi linijami. Bolj podrobno, EC in OC modelni celični liniji sintetizirata več E1 in E2 v primerjavi z ustrezno kontrolno linijo. Zadnje nakazuje aktivno vlogo estrogenov kot pro-proliferativnih in/ali kot genotoksičnih spojin pri karcinogenezi EC in OC.
Secondary keywords: rak endometrija;rak jajčnikov;sinteza estrogenov;
Type (COBISS): Master's thesis/paper
Study programme: 0
Embargo end date (OpenAIRE): 1970-01-01
Thesis comment: Univ. Ljubljana, Biotehniška fak.
Pages: XI, 61, [4] f.
ID: 12635989