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Abstract
Introduction/Background Endometrial cancer (EC) is an estrogen-dependent disease. Estrogens can be formed locally from estrone-sulfate (E1-S) which is transported into cells by organic anion-transporting polypeptides (OATP), sodium-dependent organic anion transporters (SOAT), organic anion transporters (OAT) or effluxed by ATP-binding cassette transporters (ABC) and organic solute transporter (OST) αβ (figure1). Currently, 19 transporters are known to transport E1-S but their roles in EC have not yet been determined. In our study, we analyzed the expression of these transporters in model cell lines of EC, Ishikawa and HEC-1-A, and in paired samples of EC and adjacent control tissue.
Methodology The expression of ’transporter genes’ was evaluated using qPCR and the presence of proteins was analyzed using imunocytochemistry or imunohistochemistry.
Results In cell lines and tissue samples 15 genes were differentially expressed where SLC51B, SLC51A, SLC10A6 and ABCC4 were significantly up-regulated and SLCO3A1 was significantly down-regulated in both EC cell lines compared to control endometrial cell line HIEEC. The highest difference in expression was seen for SLCO1B3 (28930.7-fold up-regulation) and ABCG2 (30.2-fold down-regulation) in HEC-1-A compared to HIEEC. Imunocytochemistry revealed significantly higher levels of OATP1B3 (SLCO1B3) (6.3-fold) in HEC-1-A compared to Ishikawa and low concentrations of ABCG2 in both EC cell lines.
In EC tissue significant changes were seen for ABCG2 and SLC51B which were significantly (3.2-fold and 2.1-fold, respectively) down-regulated and ABCC1 which was significantly (1.6-fold) up-regulated in EC tissue compared to adjacent control tissue. In patients without lymphovascular invasion gene SLCO1B3 was 15.6-fold up-regulated. Tumor grade had significant effects on expression of SLC51B, with lower levels seen in high grade cancers. Immunohistochemistry revealed significantly lower levels of ABCG2, OSTβ (SLC51B) and OATP1B3 (SLCO1B3) in EC versus control tissue.
Conclusion Our results suggest that OATP, OAT and ABC transporters have important roles in EC pathophysiology. Detailed investigation of E1-S uptake and efflux is thus in progress.
Disclosure Nothing to disclose.
Local estradiol (E2) biosynthesis in EC depends on the uptake and efflux of E1-S by transporters