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- Title
Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours.
- Authors
Buslei, Rolf; Strissel, Pamela L.; Henke, Christine; Schey, Regina; Lang, Nadine; Ruebner, Matthias; Stolt, Claus C.; Fabry, Ben; Buchfelder, Michael; Strick, Reiner
- Abstract
Aims Adenohypophysis ( AH) hormone-producing cells represent the origin of diverse groups of pituitary adenomas ( PA). Deregulation of hypothalamic hormone receptors, growth factors and cAMP signalling have been implicated in the aetiology of PA. Endogenous retroviruses ( ERVs) are derived from past exogenous retroviral infections and represent more than 8% of the human genome. Some ERV genes encode open reading frames and produce functional proteins, for example, the ERVW-1 envelope gene Syncytin-1, essential for placentogenesis, but also deregulated in human tumours. Data concerning ERV expression in the AH and related endocrine tumours are missing. Methods Syncytin-1 protein was analysed in normal AH ( n = 15) and compared with five PA subtypes ( n = 117) by immunohistochemistry. Absolute gene expression of 20 ERV functional envelope genes and ERVW-5 gag was measured. PA tissues were examined for Syncytin-1 and the cAMP signalling marker phospho- CREB- Ser133 using immunohistochemistry. Isolated primary human PA cells were treated with different hormones. Murine embryonic and adult pituitary gland ERV expressions were compared with human AH. Results Syncytin-1 protein colocalized with corticotropic cells of AH. In contrast, all PA demonstrated significant Syncytin-1 protein overexpression, supporting deregulation. All other ERV genes showed significant up-regulations in different PA subtypes. Phospho- CREB- Ser133 and Syncytin-1 colocalized in PA cells. Cultivated primary PA cells with ACTH or CRH induced their respective receptors and ERV genes. Syncytin-A/-B, murine orthologues to human Syncytin-1/-2, localized to embryonic and adult pituitary glands demonstrating functional mammalian conservation. Conclusions Deregulated ERV genes may contribute to PA development via cAMP signalling.
- Subjects
PITUITARY gland; ENDOCRINE gland tumors; ANTERIOR pituitary gland; ENDOGENOUS retroviruses; SYNCYTINS
- Publication
Neuropathology & Applied Neurobiology, 2015, Vol 41, Issue 2, p180
- ISSN
0305-1846
- Publication type
Article
- DOI
10.1111/nan.12136