ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P300

Proteomic profile of GH-secreting versus non-functioning pituitary tumors

Chiara Verpelli1, Giovanna Mantovani2, Marco Locatelli3, Lorenzo Bello3, Paolo Beck Peccoz2, Anna Spada2, Claudio Sala1 & Andrea Lania2

1CNR Institute of Neuroscience and Department of Pharmacology, University of Milan, Milano, Italy; 2Endocrine Unit, Department of Medical Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy; 3Neurosurgery, Department of Neurological Sciences, University of Milano, Fondazione IRCCS Ospedale Maggiore Policlinico, Milano, Italy.

GH-secreting and non-functioning pituitary tumors are clinically distinct, usually benign but potentially locally aggressive lesions originating from the replication of a single mutated pituitary cell. As for the underlying genetic and epigenetic alterations, also the patterns of activation of specific signaling pathways as well as the prognostic molecular factors leading to local invasiveness are, to date, largely unknown. In this study, we used two-dimensional electrophoresis and mass spectrometry to directly analyze protein profiles changes between GH-secreting (GH-omas) and non-functioning (NFPAs) pituitary tumors. In particular we analyzed 10 NFPA and 10 GH-omas surgically removed from patients not previously treated either by radiotherapy or somatostatin analogues. Proteins analysis has been performed by comparing ten gels obtained from each group of surgically eradicated tumors. Forty-two significant spots have been analyzed by mass spectrometry, resulting in the identification of eleven proteins significantly down-regulated and twenty-five proteins significantly up-regulated in non-functioning pituitary tumors in comparison to GH-secreting tumors. In particular, non-functioning pituitary tumors are characterized by a significant increase in Insulin-like growth factor-binding protein 2, Ubiquinol-cytochrome-c reductase complex core protein 1 and GTP-binding nuclear protein Ran expression. Interestingly, these proteins, whose function has not been yet investigated in human pituitary, are typically associated with a more aggressive tumor phenotype. These preliminary data to be further investigated, seem to suggest a more aggressive phenotype of non-functioning pituitary tumors compared with GH-secreting pituitary tumors. Experiments comparing the normal pituitary protein expression pattern with secreting and nonsecreting pituitary tumors are in progress.

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