Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 26 S3.3

Institute of Pathology, Helmholtz Zentrum München, München, Germany.


MENX is a recently identified multiple endocrine neoplasia (MEN) syndrome in the rat. Affected animals develop multiple neuroendocrine tumors (NETs) with high penetrance and at young age, specifically: bilateral pheochromocytoma (100%), multifocal pituitary adenoma (100%), multifocal thyroid C-cell hyperplasia, parathyroid hyperplasia, extra-adrenal pheochromocytoma (paragangliomas) and pancreatic islet cell hyperplasia. MENX is caused by a germline frameshift mutation of the Cdkn1b gene, which leads to extremely reduced expression of the encoded mutant p27 protein in vivo. Capitalizing on this discovery, we and others identified germline mutations in CDKN1B in patients having multiple endocrine tumors (the MEN4 syndrome).

In order to exploit the MENX animal model in studies aimed at elucidating the molecular pathogenesis of NETs or in preclinical therapy-response studies, it is necessary to characterize the tumors associated with this syndrome. Thus, we assessed the histo-morphological and immunohistochemical features of the rat tumors, and demonstrated that the pituitary tumors in MENX rats are non-functioning adenomas of the gonadotroph lineage. Then, we performed transcriptome analysis to identify novel molecular mechanisms involved in the rat tumors, and correlated these findings with human NETs. Using this approach we identified novel candidate molecular markers for diagnosis and targeted therapy of pheochromocytoma. Gene expression analysis of the rat pituitary tumors is still ongoing and preliminary results will be presented. In conclusion, if properly characterized and exploited the MENX syndrome may represent a relevant translational platform for molecular and preclinical studies of NETs.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts

Lessons from MENX (<1 min ago)

Authors