Role of Filamin-A in the regulation of SST2 receptor localization and signalling in tumoral GH-secreting cells

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 389-408-Signaling Originating from Membrane Receptors
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-404
Erika Peverelli*1, Elena Giardino1, Eleonora Vitali1, Valeria Cambiaghi2, Andrea Lania2, Paolo Beck-Peccoz3, Anna Spada1 and Giovanna Mantovani1
1Univ of Milan, Ospedale Maggiore Policlinico, Milan, Italy, 2IRCCS Humanitas Clinical Institute, Rozzano, Italy, 3University of Milan, Fondazione IRCCS Cą Granda-Ospedale Maggiore Policlinico, Milan, Italy
Somatostatin (SS) binds to different SS receptors (SSTR 1-5) 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.

We studied FLNA expression in tissue samples from GH-omas (N=10) by western blotting (WB). Moreover, we evaluated the role of FLNA in SSTR2 localization and signaling by gene silencing technique in primary cultured cells from 6 GH-omas. Confocal microscopy was used to detect SSTR2 intracellular localization and WB to evaluate cyclin D1 and SSTR2 expression.

We found that FLNA was expressed at variable levels in GH-oma samples, without any significant correlation with the clinical phenotype. 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 GH-secreting adenoma cultured cells 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.

Nothing to Disclose: EP, EG, EV, VC, AL, PB, AS, GM

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