雌激素受体β与相关肿瘤研究进展

Progress in Research of Estrogen Receptor Beta and Human Cancer

雌激素通过与特定的雌激素受体相互作用发挥重要的细胞生长和分化作用。雌激素受体是属于细胞核受体超家族的配体依赖性的反式作用子。尽管最初认为雌激素由单一的受体,即传统的雌激素受体,现称为ERα介导其作用,第二个ER新亚型,现称为ERβ,1996年被发现,并由此引发了一场对于雌激素在正常生理学和疾病过程的作用重新评价。自从发现ERβ以来,其作为相关肿瘤的预警因子以及其潜在的作为药物介入的新靶点的价值成为研究热点。在过去的10年中,我们对雌激素信号的理解有很大改变。现在,已知ERα和ERβ组织细胞分布和功能不同。ERβ存在于许多正常和疾病组织中,包括生殖系统和其他组织器官的恶性肿瘤,如乳腺、子宫内膜、卵巢、前列腺和结肠直肠癌以及其他肿瘤。因此,ERβ在这些肿瘤的发生发展和治疗方面的作用引起了人们越来越多的关注。现就ERβ在雌激素相关肿瘤的发生、发展、预后评估以及治疗意义进行综述。

Estrogens, via the interaction with their receptors, play important roles in the control of cellular growth and differentiation. Estrogen receptors belong to a superfamily of nuclear receptors that are ligand-dependent transactivators. Although it was initially thought that estrogens mediate their action through a single receptor, the estrogen receptor alpha （ERα）. A second ER was identified in 1996, termed estrogen receptor beta （ERβ） and it has led to an intensive re-evaluation of the role of estrogen and antiestrogen signaling in normal physiological and disease processes. Ever since the ERβ was discovered, its value as a prognostic or predictive factor in cancer and its potential as a novel target for pharmacological intervention are being investigated. During the past 10 years, our understanding of estrogen signaling has changed remarkably. Today we have known that ERα and ERβ have distinct cellular distributions and are functionally distinct. ERβ has been described in numerous normal and pathological tissues, including reproductive malignancies and other cancers such as breast, endometrial, ovarian, prostatic and colorectal as well as in other tumors. This finding has raised questions about the role of ERβ in the development and treatment of these cancers. The present review is devoted to the discussion of these recent findings on the value of the expression of ERβ in carcinogenesis and cancer development and as a possible target for prognostic significance and therapeutic implications in estrogen-related cancer.