Role of the aryl hydrocarbon receptor-interacting protein in familial isolated pituitary adenoma

Abstract

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.

Keywords::

• AhR
• AIP
• aryl hydrocarbon receptor
• aryl hydrocarbon receptor-interacting protein
• familial isolated pituitary adenoma
• FIPA
• PAP
• pituitary adenoma
• pituitary adenoma predisposition
• tumor-suppressor gene

Financial & competing interests disclosure

Joshua W Cain was supported by the Wolfson foundation and the Association of Physicians of Great Britain and Ireland. Our laboratories’ FIPA project is supported by the Cancer Research Committee of St Bartholomew’s Hospital (London, UK). The FIPA project in Serbia was supported by a grant from the Ministry of Science (145019). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.