Yates Christopher J, Lines Kate E, Thakker Rajesh V
a 1 Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, Churchill Hospital, Oxford, Oxfordshire, OX3 7LJ, UK.
b 2 Department of Diabetes and Endocrinology, Melbourne Health, The Royal Melbourne Hospital, Grattan Street, Parkville, Vic 3050, Australia.
Expert Rev Endocrinol Metab. 2015 Jan;10(1):35-53. doi: 10.1586/17446651.2015.955795. Epub 2014 Sep 2.
Pituitary adenomas are a heterogeneous group of tumors that may occur as part of a complex syndrome or as an isolated endocrinopathy and both forms can be familial or non-familial. Studies of syndromic and non-syndromic pituitary adenomas have yielded important insights about the molecular mechanisms underlying tumorigenesis. Thus, syndromic forms, including multiple endocrine neoplasia type 1 (MEN1), MEN4, Carney Complex and McCune Albright syndrome, have been shown to be due to mutations of the tumor-suppressor protein menin, a cyclin-dependent kinase inhibitor (p27), the protein kinase A regulatory subunit 1-α, and the G-protein α-stimulatory subunit (Gsα), respectively. Non-syndromic forms, which include familial isolated pituitary adenoma (FIPA) and sporadic tumors, have been shown to be due to abnormalities of: the aryl hydrocarbon receptor-interacting protein; Gsα; signal transducers; cell cycle regulators; transcriptional modulators and miRNAs. The roles of these molecular abnormalities and epigenetic mechanisms in pituitary tumorigenesis, and their therapeutic implications are reviewed.
垂体腺瘤是一组异质性肿瘤，可作为复杂综合征的一部分出现，也可作为孤立性内分泌病出现，这两种形式都可以是家族性或非家族性的。对综合征性和非综合征性垂体腺瘤的研究为肿瘤发生的分子机制提供了重要见解。因此，已证明综合征形式，包括1型多发性内分泌肿瘤（MEN1）、MEN4、卡尼综合征和麦库恩-奥尔布赖特综合征，分别是由于肿瘤抑制蛋白menin、细胞周期蛋白依赖性激酶抑制剂（p27）、蛋白激酶A调节亚基1-α和G蛋白α刺激亚基（Gsα）的突变所致。非综合征形式，包括家族性孤立性垂体腺瘤（FIPA）和散发性肿瘤，已证明是由于以下异常所致：芳烃受体相互作用蛋白；Gsα；信号转导子；细胞周期调节因子；转录调节因子和微小RNA。本文综述了这些分子异常和表观遗传机制在垂体肿瘤发生中的作用及其治疗意义。
