Altered Profile of E1-S Transporters in Endometrial Cancer: Lower Protein Levels of ABCG2 and OSTβ and Up-Regulation of SLCO1B3 Expression
Copyright policy )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.
- University of Ljubljana Slovenia
- University Medical Centre Ljubljana Slovenia
- University of Vienna Austria
Fluorescent Antibody Technique, Organic Anion Transporters, Subfamily G, GUIDELINES, Neoplasm Proteins/genetics, ATP Binding Cassette Transporter, Subfamily G, Member 2, Membrane Transport Proteins/genetics, E1-S transporters, info:eu-repo/classification/udc/618.1, Tumor, Age Factors, Organic solute transporters, Intracrinology, Immunohistochemistry, rak endometrija, Neoplasm Proteins, Organic Anion Transporters/genetics, Gene Expression Regulation, Neoplastic, Postmenopause, SDG 3 – Gesundheit und Wohlergehen, Multigene Family, endometrial cancer, HORMONES, Female, Estrone-sulphate (E1-S), LOCALIZES, Estrone, 301212 Clinical pharmacy, ATP Binding Cassette Transporter, Estrone/analogs & derivatives, intrakrinologija, intracrinology, organski polipeptidi, VALIDATION, Article, Cell Line, Solute Carrier Organic Anion Transporter Family Member 1B3, estrone-sulphate (E1-S), SDG 3 - Good Health and Well-being, SULFATASE, Cell Line, Tumor, ki prenašajo anione, Organic anion-transporting polypeptides, Humans, organic anion-transporting polypeptides, Neoplasm Invasiveness, 301212 Klinische Pharmazie, Sulfatase pathway, NUCLEUS, Neoplasm Staging, Neoplastic, Member 2/genetics, Membrane Transport Proteins, ATP-binding cassette transporters, Biological Transport, organic solute transporters, Endometrial Neoplasms, Gene Expression Regulation, IMPORTANT ROLES, CELLS, Solute Carrier Organic Anion Transporter Family Member 1B3/genetics, Neoplasm Grading, Endometrial Neoplasms/genetics, sulfatase pathway
Fluorescent Antibody Technique, Organic Anion Transporters, Subfamily G, GUIDELINES, Neoplasm Proteins/genetics, ATP Binding Cassette Transporter, Subfamily G, Member 2, Membrane Transport Proteins/genetics, E1-S transporters, info:eu-repo/classification/udc/618.1, Tumor, Age Factors, Organic solute transporters, Intracrinology, Immunohistochemistry, rak endometrija, Neoplasm Proteins, Organic Anion Transporters/genetics, Gene Expression Regulation, Neoplastic, Postmenopause, SDG 3 – Gesundheit und Wohlergehen, Multigene Family, endometrial cancer, HORMONES, Female, Estrone-sulphate (E1-S), LOCALIZES, Estrone, 301212 Clinical pharmacy, ATP Binding Cassette Transporter, Estrone/analogs & derivatives, intrakrinologija, intracrinology, organski polipeptidi, VALIDATION, Article, Cell Line, Solute Carrier Organic Anion Transporter Family Member 1B3, estrone-sulphate (E1-S), SDG 3 - Good Health and Well-being, SULFATASE, Cell Line, Tumor, ki prenašajo anione, Organic anion-transporting polypeptides, Humans, organic anion-transporting polypeptides, Neoplasm Invasiveness, 301212 Klinische Pharmazie, Sulfatase pathway, NUCLEUS, Neoplasm Staging, Neoplastic, Member 2/genetics, Membrane Transport Proteins, ATP-binding cassette transporters, Biological Transport, organic solute transporters, Endometrial Neoplasms, Gene Expression Regulation, IMPORTANT ROLES, CELLS, Solute Carrier Organic Anion Transporter Family Member 1B3/genetics, Neoplasm Grading, Endometrial Neoplasms/genetics, sulfatase pathway
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