Altered profile of E1-S transporters in endometrial cancer

lower protein levels of ABCG2 and OST[beta] and up-regulation of SLCO1B3 expression

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

Abstract

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)alfa, beta. 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 (OSTbeta) 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.

Keywords

rak endometrija;intrakrinologija;organski polipeptidi, ki prenašajo anione;endometrial cancer;intracrinology;organic anion-transporting polypeptides;

Data

Language:	English
Year of publishing:	2021
Typology:	1.01 - Original Scientific Article
Organization:	UL MF - Faculty of Medicine
UDC:	618.1
COBISS:	58810371
ISSN:	1422-0067
Views:	200
Downloads:	47
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	rak endometrija;intrakrinologija;organski polipeptidi;ki prenašajo anione;
Type (COBISS):	Article
Pages:	str. 1-27
Volume:	ǂVol. ǂ22
Issue:	ǂiss. ǂ8
Chronology:	2021
DOI:	10.3390/ijms22083819
ID:	14704352