ECE2013 Poster Presentations Pituitary–Basic (<emphasis role="italic">Generously supported by IPSEN</emphasis>) (17 abstracts)
Role of filamin-A in the regulation of SST2 receptor localization and signalling in tumoral GH-secreting cells
Elena Giardino 1 , Erika Peverelli 1 , Eleonora Vitali 1 , Valeria Cambiaghi 1, , Andrea G Lania 1, , Paolo Beck Peccoz 1 , Giovanna Mantovani 1 & Anna Spada 1
1Endocrine Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; 2Endocrine Unit, IRCCS Humanitas Clinical Institute, Rozzano, Italy.
Somatostatin (SS) binds to different SS receptors (SSTR1–5) and SS analogues are the first choice medical treatment of GH-secreting pituitary adenomas (GH-omas). A subset of patients is resistant to SS, although the mechanisms involved in SS resistance are not fully understood. Recent studies identified specific protein–protein interactions as determinant in the regulation of receptor anchoring and signalling. Filamin A (FLNA) is a widely expressed cytoskeleton protein that, through its scaffolding properties, affects the intracellular signalling and trafficking of a number of receptors. Based on our recently published data, FLNA is crucial for D2 receptor expression and signalling in lactotrophs cells. Since SSTR2 was recently found to associate with FLNA, the aim of this study was to investigate the role of FLNA in SSTR2 signalling and targeting in human GH-omas and GH3, a rat pituitary GH-secreting cell line.
We studied FLNA expression in GH-omas (n=10) by western blotting (WB) and its role in GH3 by gene silencing technique. Confocal microscopy was used to evaluate receptor SSTR2 localization and WB to evaluated cyclin CD1 and SST2R expression.
In all GH-omas FLNA was expressed at variable levels, without any significant correlation with the clinical phenotype. In GH3 cells FLNA gene silencing did not induce changes in SSTR2 total levels. Similarly, this manipulation did not affect receptor localization at the plasma membrane. On the contrary, the reduction in cyclin D1 levels induced by the selective SSTR2 agonist (Bim23120) in GH3 was abolished in FLNA silenced cells.
These data suggest that FLNA might be implicated in intracellular signalling of SSTR2 by mediating at least some of its antiproliferative effects. In contrast, FLNA does not appear to be necessary for receptor expression and localization at the plasma membrane.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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