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雌激素参与调节女性多种生殖或非生殖组织的正常生长、分化和运行。外源雌激素(xenoestrogen,XEs)的介入干扰机体内正常的生理平衡,并在具有雌激素依赖性细胞中通过雌激素受体(estrogen receptor,ER)介导基因组和非基因组途径发挥雌激素效应。然而,膜雌激素受体,特别是ER-α36介导XEs产生的非基因组途径因其低剂量、低亲和力、非线性、快速信号转导、整合等效应而备受关注。在XEs的刺激下,ER-α36可通过非基因组途径激活cAMP、PKC、Ca~(2+)、MAPK/ERK、PI3K/Akt等下游通路诱导产生雌激素效应。研究ER-α36和肿瘤细胞的相关性对肿瘤的发生和治疗具有重要意义。重点介绍ER-α36在子宫内膜癌、乳腺癌和卵巢癌等妇科肿瘤中介导非基因组产生的雌激素效应及其在疾病治疗过程中产生的影响,以期为妇科肿瘤预防和治疗提供一定的理论指导。
Estrogen is involved in regulating the normal growth, differentiation, and functioning of multiple female or non-reproductive tissues. Intervention with xenoestrogen (XEs) interferes with the normal physiological homeostasis and exerts estrogenic effects in estrogen-dependent cells via genomic and non-genomic pathways mediated by the estrogen receptor (ER) . However, non-genomic pathways mediated by membrane-estrogen receptors, especially ER-α36, have drawn much attention due to their low dose, low affinity, nonlinearity, rapid signal transduction and integration. Under the stimulation of XEs, ER-α36 can induce the estrogen effect by activating downstream pathways of cAMP, PKC, Ca 2+, MAPK / ERK and PI3K / Akt through non-genomic pathway. The study of the correlation between ER-α36 and tumor cells is of great significance for the occurrence and treatment of tumors. It focuses on the estrogen effect of non-genomic production mediated by ER-α36 in gynecological tumors such as endometrial cancer, breast cancer and ovarian cancer and its influence on the course of disease treatment, so as to provide some evidences for the prevention and treatment of gynecologic oncology Theoretical guidance.