Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours

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Details zur Publikation

Autor(en): Buslei R, Strissel P, Henke C, Schey R, Lang N, Ruebner M, Stolt C, Fabry B, Buchfelder M, Strick R
Zeitschrift: Neuropathology and Applied Neurobiology
Verlag: Wiley-Blackwell
Jahr der Veröffentlichung: 2015
Band: 41
Heftnummer: 2
Seitenbereich: 180-200
ISSN: 0305-1846


Abstract


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.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.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.Deregulated ERV genes may contribute to PA development via cAMP signalling.



FAU-Autoren / FAU-Herausgeber

Buchfelder, Michael Prof. Dr.
Lehrstuhl für Neurochirurgie
Fabry, Ben Prof. Dr.
Lehrstuhl für Biophysik
Henke, Christine
Frauenklinik
Lang, Nadine
Lehrstuhl für Biophysik
Schey, Regina
Professur für Medizinische Mikrobiologie und Infektionsimmunologie
Stolt, Claus PD Dr.
Lehrstuhl für Biochemie und Pathobiochemie
Strick, Reiner Prof. Dr.
Medizinische Fakultät
Strissel, Pamela PD Dr.
Medizinische Fakultät


Zitierweisen

APA:
Buslei, R., Strissel, P., Henke, C., Schey, R., Lang, N., Ruebner, M.,... Strick, R. (2015). Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours. Neuropathology and Applied Neurobiology, 41(2), 180-200. https://dx.doi.org/10.1111/nan.12136

MLA:
Buslei, R., et al. "Activation and regulation of endogenous retroviral genes in the human pituitary gland and related endocrine tumours." Neuropathology and Applied Neurobiology 41.2 (2015): 180-200.

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Zuletzt aktualisiert 2018-05-10 um 02:30