Department of Haematology, Oslo University Hospital, Oslo, Norway.
Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
Thromb Haemost. 2022 Aug;122(8):1288-1295. doi: 10.1055/a-1707-2130. Epub 2021 Nov 26.
Most breast cancers express estrogen receptor (ER) where estrogen signaling plays an important role. Cancer contributes to activation of the coagulation system leading to an imbalance in the hemostatic system, and coagulation factor (F) V, which is a key regulator of blood coagulation, has been shown to be increased in breast tumors. Thus, the molecular association between estrogens and FV was explored. Stimulation with 17-β-estradiol (E2) or 17-β-ethinylestradiol (EE2) resulted in a time- and dose-dependent increase in messenger RNA and FV protein in ERα-positive MCF-7 cells. Pretreatment with the ER antagonist fulvestrant or knockdown of ERα prior to stimulation with E2 counteracted this effect. Three ERα-binding half-sites were identified in the promoter region of the gene . Reporter gene analysis showed that all three half-sites were involved in the estrogen-induced gene regulation , as the effect was abolished only when all half-sites were mutated. High levels in ER-positive breast tumors were associated with increased relapse-free survival of breast cancer patients.
大多数乳腺癌表达雌激素受体（ER），雌激素信号在其中发挥重要作用。癌症会导致凝血系统激活，导致止血系统失衡，凝血因子（F）V 是血液凝固的关键调节剂，已被证明在乳腺癌肿瘤中增加。因此，探索了雌激素和 FV 之间的分子关联。用 17-β-雌二醇（E2）或 17-β-乙炔雌二醇（EE2）刺激导致 ERα 阳性 MCF-7 细胞中的信使 RNA 和 FV 蛋白呈时间和剂量依赖性增加。用 ER 拮抗剂氟维司群预处理或在用 E2 刺激之前敲低 ERα 可抵消这种作用。在 基因的启动子区域中鉴定出三个 ERα 结合半位点。报告基因分析表明，所有三个半位点都参与了雌激素诱导的基因调控，因为只有当所有半位点都发生突变时，这种作用才会被消除。在 ER 阳性乳腺癌肿瘤中高表达与乳腺癌患者无复发生存率的增加相关。
