Altered profile of E1-S transporters in endometrial cancer : lower protein levels of ABCG2 and OSTβ and up-regulation of SLCO1B3 expression

Pavlič, Renata (author), Vidic, Suzana (author), Anko, Maja (author), Knific, Tamara (author), Büdefeld, Tomaž (author), Marton, Kristina (author), Sinreih, Maša (author), Poschner, Stefan (author), Jäger, Walter (author), Frković-Grazio, Snježana (author), Lanišnik-Rižner, Tea (author)

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.

• Language: English
• Keywords: endometrial cancer, intracrinology, organic anion-transporting polypeptides, estrone-sulphate (E1-S), sulfatase pathway, E1-S transporters, ATP-binding cassette transporters, organic solute transporters
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 26 str.
• Numbering: Vol. 22, iss. 8, art. 3819
• PID: 20.500.12556/RUL-135333
• UDC: 618.1
• ISSN on article: 1422-0067
• DOI: 10.3390/ijms22083819
• COBISS.SI-ID: 58810371
• Publication date in RUL: 08.03.2022

Record is a part of a journal

• Title: International journal of molecular sciences
• Shortened title: Int. j. mol. sci.
• Publisher: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 07.04.2021

Secondary language

• Language: Slovenian
• Keywords: rak endometrija, intrakrinologija, organski polipeptidi, ki prenašajo anione