Synthesis of estrogens in cell lines of endometrial and ovarian cancer

Gjorgoska, Marija (avtor), Lanišnik Rižner, Tea (mentor), Sinreih, Maša (komentor)

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 model cell lines of EC and OC 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 E1 and E2 are synthesized in the EC and OC model cell lines comparing to the respective control lines, altogether implying an active role of estrogen in EC and OC carcinogenesis, acting as pro-proliferative hormones and/or genotoxic agents.

• Jezik: Angleški jezik
• Ključne besede: endometrial cancer, ovarian cancer, estrogen formation, liquid chromatography, tandem mass spectrometry
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: BF - Biotehniška fakulteta
• Leto izida: 2021
• PID: 20.500.12556/RUL-125327
• COBISS.SI-ID: 55705859
• Datum objave v RUL: 11.03.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Naslov: Sinteza estrogenov v celičnih linijah raka endometrija in jajčnikov

Izvleček

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.

• Ključne besede: rak endometrija, rak jajčnikov, sinteza estrogenov, tekočinska kromatografija, masna spektrometrija