FLNA expression modulates pathological markers of pituitary neuroendocrine tumours

in Journal of Endocrinology
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Jonathan Toledo Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Córdoba, Argentina
Centro de Microscopia Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

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Pablo Aníbal Perez Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Córdoba, Argentina
Centro de Microscopia Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

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Mical Zanetti Centro de Microscopia Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

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Graciela Díaz-Torga Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina

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Jorge Humberto Mukdsi Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Córdoba, Argentina
Centro de Microscopia Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

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Silvina Gutierrez Instituto de Investigaciones en Ciencias de la Salud (INICSA-CONICET), Córdoba, Argentina
Centro de Microscopia Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina

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Correspondence should be addressed to S Gutierrez: silvina@cmefcm.uncor.edu
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Due to the current limited knowledge about the role of filamin A (FLNA) in pituitary tumour progression, we aimed to analyse FLNA expression levels and its impact on aggressive markers of pituitary neuroendocrine tumours (PitNETs), using an integrative approach of in vivo and in vitro models and human samples. An increase in the expression levels of FLNA was observed in the advanced tumoural stages of the hyperplastic adenomatous pituitary model, concomitant with a decrease in cell proliferation and with a modification in the subcellular localisation of this protein. Similarly, overexpression of FLNA in the somatolactotropic GH3 cell line induced a decrease in the cell proliferation, promoted a migratory phenotype, increased invasion activity, and decreased the prolactin secretion. Cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4) expression increased in both models in correlation with the increase observed in FLNA levels. When human tissues were analysed a significant increase of FLNA was observed in PitNETs compared to normal pituitary gland, with heterogeneous intracellular localisation. Higher levels of FLNA expression were observed in tumours with invasive characteristics. These results underline the crucial roles of FLNA as a modulator of pathological markers and as a potential prognostic marker in pituitary tumours.

 

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