20.500.12556/RUL-135333 Altered profile of E1-S transporters in endometrial cancer lower protein levels of ABCG2 and OSTβ and up-regulation of SLCO1B3 expression Endometrial cancer (EC) is associated with increased estrogen actions. Locally, estrogens can be formed from estrone-sulphate (E1-S) after cellular uptake by organic anion-transporting polypeptides (OATP) or organic anion transporters (OAT). Efflux of E1-S is enabled by ATP Binding Cassette transporters (ABC) and organic solute transporter (OST)αβ. Currently, 19 E1-S transporters are known but their roles in EC are not yet understood. Here, we analysed levels of E1-S transporters in Ishikawa (premenopausal EC), HEC-1-A (postmenopausal EC), HIEEC (control) cell lines, in EC tissue, examined metabolism of steroid precursor E1-S, studied effects of OATPs’ inhibition and gene-silencing on E1-S uptake, and assessed associations between transporters and histopathological data. Results revealed enhanced E1-S metabolism in HEC-1-A versus Ishikawa which could be explained by higher levels of OATPs in HEC-1-A versus Ishikawa, especially 6.3-fold up-regulation of OATP1B3 (SLCO1B3), as also confirmed by immunocytochemical staining and gene silencing studies, lower ABCG2 expression and higher levels of sulfatase (STS). In EC versus adjacent control tissue the highest differences were seen for ABCG2 and SLC51B (OSTβ) which were 3.0-fold and 2.1-fold down-regulated, respectively. Immunohistochemistry confirmed lower levels of these two transporters in EC versus adjacent control tissue. Further analysis of histopathological data indicated that SLCO1B3 might be important for uptake of E1-S in tumours without lymphovascular invasion where it was 15.6-fold up-regulated as compared to adjacent control tissue. Our results clearly indicate the importance of E1-S transporters in EC pathophysiology and provide a base for further studies towards development of targeted treatment. endometrial cancer intracrinology organic anion-transporting polypeptides estrone-sulphate (E1-S) sulfatase pathway E1-S transporters ATP-binding cassette transporters organic solute transporters rak endometrija intrakrinologija organski polipeptidi ki prenašajo anione true false true Angleški jezik Slovenski jezik Članek v reviji 2022-03-08 10:20:54 2022-03-08 10:20:57 2022-09-14 04:12:50 0000-00-00 00:00:00 2021 0 0 26 str. iss. 8, art. 3819 Vol. 22 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 618.1 1422-0067 10.3390/ijms22083819 58810371 RAZ_Pavlic_Renata_2021.pdf RAZ_Pavlic_Renata_2021.pdf 1 786DE74B6841DD8B38B68A2D2513FFFE b13833748cf6289c80f7b6dd7a6238fc85ade2d633dba64f60502727fa3927df 62a42da3-9ec1-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154350 https://www.mdpi.com/1422-0067/22/8/3819 1 c927e94b-9ec0-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=154348 Medicinska fakulteta 0 0 0