Role of Estrogen Receptor-α in the Regulation of Claudin-6 Expression in Breast Cancer Cells

Purpose In our previous studies we showed that upregulating claudin-6 (CLDN6) expression may contribute to preventing breast cancer, and that 17 beta-estradiol induces a concentration-and time-related effect on CLDN6 mRNA and protein expression in MCF-7 cells. However, the mechanisms of 17 beta-estradiol regulation of CLDN6 are still unclear. We determined the role of estrogen receptors in the regulation of CLDN6 expression in human breast cancer tissues and a cell line. Methods: CLDN6, estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta) expression in breast cancer tissues were examined using immunohistochemistry. The human breast cancer cell line, MCF-7, which expresses ER alpha but not ER beta was used. CLDN6 and ER alpha expression were measured by reverse transcriptase-PCR, Western blotting and immunofluorescent staining. Treatments with propyl pyrazole triol (PPT) and 101 182, 780 (ICI) were performed. Result: The results revealed that CLDN6 expression was related to ER alpha in breast cancer tissues (p = 0.033). PPT, an ER alpha-selective ligand, upregulated CLDN6 expression at 10(-5) mol/L after 24 hours. The effect of PPT on regulating CLDN6 expression in MCF-7 cells was blocked by ICI. Conclusion: These findings suggest that Er alpha reulates CLDN6 expression in breast cancer tissues and that 17 beta-estradiol induces CLDN6 expression through an ER alpha pathway in MCF-7 cells.