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Characterization of MENX-associated pituitary tumours.
Neuropathol. Appl. Neurobiol. 39, 256-269 (2013)
Aims: The aim of this study is to evaluate the pathological features, serum hormone levels and ex-vivo cultures of pituitary adenomas that occur in rats affected by MENX syndrome. MENX is multiple endocrine neoplasia syndrome caused by a germline mutation in the cell cycle inhibitor p27. Characterisation of MENX adenomas is a prerequisite to exploit this animal model for molecular and translational studies of pituitary adenomas. Methods: We investigated MENX pituitary adenomas with immunohistochemistry, double immunofluorescence, electron microscopy, RT-PCR, measurement of serum hormone levels and ex-vivo cultures. Results: Adenomas in MENX rats belong to the gonadotroph lineage. They start from 4 months of age as multiple neoplastic nodules and progress to become large lesions that efface the gland. Adenomas are composed of chromophobic cells predominantly expressing the glycoprotein alpha-subunit (αGSU). They show mitotic activity and high Ki67 labelling. A few neoplastic cells co-express gonadotrophins and the transcription factor SF1, together with growth hormone or prolactin and Pit-1, suggesting that they are not fully committed to one cell lineage. Ex vivo cultures show features similar to the primary tumour. Conclusions: Our results suggest that p27 function is critical in regulating gonadotroph cells growth. The MENX syndrome represents a unique model to elucidate the physiological and molecular mechanisms mediating the pathogenesis of gonadotroph adenomas.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter MENX; Pituitary adenoma; Gonadotroph; Animal model; p27; Multiple Endocrine Neoplasia ; Cycle Inhibitor P27(kip1) ; Hormone Beta-subunit ; Sprague-dawley Rats ; Gonadotroph Adenomas ; Transgenic Mice ; Alpha-subunit ; Hyperplasia ; Tumorigenesis ; Expression
ISSN (print) / ISBN 0305-1846
Zeitschrift Neuropathology and Applied Neurobiology
Quellenangaben Band: 39, Heft: 3, Seiten: 256-269
Begutachtungsstatus Peer reviewed