Cain Joshua W, Miljic Dragana, Popovic Vera, Korbonits Márta
a Department of Endocrinology, Barts and the London School of Medicine, Queen Mary University of London, EC1M 6BQ, UK.
b Institute of Endocrinology, School of Medicine, University Belgrade Belgrade, Serbia.
Expert Rev Endocrinol Metab. 2010 Sep;5(5):681-695. doi: 10.1586/eem.10.42.
Pituitary adenomas are typically sporadic benign tumors. However, approximately 5% of cases have been found to be familial in origin. Of these, approximately 40% occur in the absence of multiple endocrine neoplasia type 1 or Carney complex and have been termed 'familial isolated pituitary adenoma' (FIPA). Recently, germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been described in 15-20% of these families, identifying an autosomal dominant condition with incomplete penetrance termed 'pituitary adenoma predisposition'. Pituitary adenoma predisposition cohorts show a marked disposition to develop large, aggressive somatotroph, somatolactotroph or lactotroph adenomas, typically presenting at a young age. AIP mutation families have a distinct clinical phenotype compared with AIP mutation-negative FIPA families. Current evidence suggests that AIP is a tumor-suppressor gene. AIP has been demonstrated to interact with a number of cellular proteins, including several nuclear receptors, heat-shock protein 90 and survivin, although the mechanism of the tumor-suppressor effect is unknown. This article summarizes available data regarding the role of AIP in pituitary tumorigenesis and the clinical features of FIPA.
垂体腺瘤通常为散发性良性肿瘤。然而，约5%的病例被发现有家族性起源。其中，约40%发生于无1型多发性内分泌腺瘤或卡尼综合征的情况下，被称为“家族性孤立性垂体腺瘤”（FIPA）。最近，在这些家族中15% - 20%的病例中发现了芳香烃受体相互作用蛋白（AIP）基因的种系突变，确定了一种具有不完全外显率的常染色体显性疾病，称为“垂体腺瘤易感性”。垂体腺瘤易感性队列显示出明显倾向于发生大的、侵袭性的生长激素细胞、生长激素泌乳素细胞或泌乳素细胞腺瘤，通常在年轻时发病。与AIP突变阴性的FIPA家族相比，AIP突变家族具有独特的临床表型。目前的证据表明AIP是一种肿瘤抑制基因。尽管肿瘤抑制作用的机制尚不清楚，但已证明AIP与多种细胞蛋白相互作用，包括几种核受体、热休克蛋白90和生存素。本文总结了有关AIP在垂体肿瘤发生中的作用以及FIPA临床特征的现有数据。
