端粒酶和端粒在子宫内膜癌中的作用
由于“末端复制问题”以及氧化应激,每轮细胞分裂都会缩短人类染色体末端的端粒。在致癌过程中,细胞获得或保持端粒的机制,从而避免细胞衰老或凋亡的发生,并通过临界短端粒来阻止细胞分裂。独特的逆转录酶复合物端粒酶催化端粒的维持,但是大多数人类体细胞没有足够的端粒酶活性来阻止端粒缩短。具有高且长期复制潜能的组织显示出足够的细胞端粒酶活性来防止端粒侵蚀,而端粒酶高活性似乎是大多数(80-90%)上皮癌(包括子宫内膜癌)的关键特征。子宫内膜癌对孕酮的反应会消退,黄体酮通常用于治疗晚期子宫内膜癌。子宫内膜端粒酶受到孕激素的抑制,端粒的破译和端粒酶生物学在子宫内膜癌中很重要,因为在子宫内膜癌中靶向端粒酶(孕激素的下游靶标)可能提供新颖且更有效的治疗途径。这项审查旨在检查端粒和端粒酶生物学在子宫内膜癌中的作用和重要性的可用证据。**
Telomerase and Telomeres in Endometrial Cancer
Telomeres at the termini of human chromosomes are shortened with each round of cell division due to the "end replication problem" as well as oxidative stress. During carcinogenesis, cells acquire or retain mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis and halting cell division by critically short telomeres. The unique reverse transcriptase enzyme complex, telomerase, catalyzes the maintenance of telomeres but most human somatic cells do not have sufficient telomerase activity to prevent telomere shortening. Tissues with high and prolonged replicative potential demonstrate adequate cellular telomerase activity to prevent telomere erosion, and high telomerase activity appears to be a critical feature of most (80-90%) epithelial cancers, including endometrial cancer. Endometrial cancers regress in response to progesterone which is frequently used to treat advanced endometrial cancer. Endometrial telomerase is inhibited by progestogens and deciphering telomere and telomerase biology in endometrial cancer is therefore important, as targeting telomerase (a downstream target of progestogens) in endometrial cancer may provide novel and more effective therapeutic avenues. This review aims to examine the available evidence for the role and importance of telomere and telomerase biology in endometrial cancer.
pmid: 31157162 Front Oncol 影响因子: 4.137 发表日期: 20190101 官网 免费下载
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