Estrogen Receptor Signaling and Crosstalk with the Ah Receptor in Endometrial Cancer Cells

摘要: Common risk factors for the development of endometrial and breast cancer include early menarche, late menopause, null parity, later age at first birth, indicating that “lifetime” exposure to estrogens increases incidence both tumors. In contrast, smoking protects against cancer, whereas role in is equivocal may be dependent on timing duration smoking. Constituents cigarette smoke bind activate aryl hydrocarbon receptor (AhR), research this laboratory has focused characterizing inhibitory AhR-estrogen (ER) a crosstalk cell lines. Both Ishikawa ECC1 cells express AhR ERoc proteins by Western blot analysis. Moreover, ligands such as benzo[a]pyrene (BaP) and/or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induce CYP1A1-dependent activity or reporter gene transfected with constructs containing dioxin-responsive elements promoters. Estrogen responsiveness was also confirmed these cells, evidenced gene/reporter assay induction proliferation 17β-estradiol (E2). Inhibitory AhR-ERα studies have shown TCDD BaP inhibit E2-induced growth block hormone-activated gene/gene responses. Although there are several possible mechanisms interaction between ERα signaling pathways, AhR-mediated downregulation will discussed one mechanism. addition, selective modulators been developed treatment potential use compounds alone combination tamoxifen outlined.