Caiazza Francesco, Ryan Elizabeth J, Doherty Glen, Winter Desmond C, Sheahan Kieran
Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Science, University College , Dublin , Ireland.
Centre for Colorectal Disease, Saint Vincent's University Hospital , Dublin , Ireland ; Department of Surgery, St. Vincent's University Hospital, Elm Park , Dublin , Ireland.
Front Oncol. 2015 Feb 2;5:19. doi: 10.3389/fonc.2015.00019. eCollection 2015.
Upon binding their cognate receptors, ERα (ESR1) and ERβ (ESR2), estrogens activate intracellular signaling cascades that have important consequences for cellular behavior. Historically linked to carcinogenesis in reproductive organs, estrogens have also been implicated in the pathogenesis of different cancer types of non-reproductive tissues including the colon. ERβ is the predominant estrogen receptor expressed in both normal and malignant colonic epithelium. However, during colon cancer progression, ERβ expression is lost, suggesting that estrogen signaling may play a role in disease progression. Estrogens may in fact exert an anti-tumor effect through selective activation of pro-apoptotic signaling mediated by ERβ, inhibition of inflammatory signals and modulation of the tumor microenvironment. In this review, we analyze the estrogen pathway as a possible therapeutic avenue in colorectal cancer, we report the most recent experimental evidence to explain the cellular and molecular mechanisms of estrogen-mediated protection against colorectal tumorigenesis, and we discuss future challenges and potential avenues for targeted therapy.
雌激素与它们的同源受体ERα（ESR1）和ERβ（ESR2）结合后，会激活细胞内信号级联反应，这对细胞行为具有重要影响。雌激素在历史上与生殖器官的致癌作用相关，同时也被认为与包括结肠在内的非生殖组织的不同癌症类型的发病机制有关。ERβ是正常和恶性结肠上皮中表达的主要雌激素受体。然而，在结肠癌进展过程中，ERβ表达会丧失，这表明雌激素信号可能在疾病进展中发挥作用。事实上，雌激素可能通过选择性激活由ERβ介导的促凋亡信号、抑制炎症信号以及调节肿瘤微环境来发挥抗肿瘤作用。在这篇综述中，我们分析了雌激素途径作为结直肠癌可能的治疗途径，报告了最新的实验证据以解释雌激素介导的预防结直肠癌发生的细胞和分子机制，并讨论了未来的挑战和靶向治疗的潜在途径。
