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Clinical significance of filamin A in patients with acromegaly and its association with somatostatin and dopamine receptor profiles.

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2018-11-30

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Coelho, Maria Caroline Alves
Vasquez, Marina Lipkin
Wildemberg, Luiz Eduardo
Vazquez-Borrego, Mari C
Bitana, Luciana
Camacho, Aline Helen da Silva
Silva, Debora
Ogino, Liana Lumi
Ventura, Nina
Sanchez-Sanchez, Rafael

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Nature Publishing Group
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Filamin-A (FLNA) plays a crucial role in somatostatin receptor (sst) subtype-2 signaling in somatotropinomas. Our objective was to investigate the in vivo association between FLNA and sst2 expression, sst5 expression, dopamine receptor subtype-2 (D2) expression, somatostatin receptor ligand (SRL) responsiveness and tumor invasiveness in somatotropinomas. Quantitative real-time PCR was used to evaluate the absolute mRNA copy numbers of FLNA/sst2/sst5/D2 in 96 somatotropinomas. FLNA, sst2 and sst5 protein expression levels were also evaluated using immunohistochemistry. The Knosp-Steiner criteria were used to evaluate tumor invasiveness. Median FLNA, sst2, sst5 and D2 copy numbers were 4,244, 731, 156 and 3,989, respectively. Thirty-one of the 35 available tumors (89%) were immune positive for FLNA in the cytoplasm and membrane but not in the nucleus. FLNA and sst5 expression were positively correlated at the mRNA and protein levels (p <0.001 and p=0.033, respectively). FLNA was positively correlated with sst2 mRNA in patients who were responsive to SRL (p=0.014, R=0.659). No association was found between FLNA and tumor invasiveness. Our fndings show that in somatotropinomas FLNA expression positively correlated with in vivo sst5 and D2 expression. Notably, FLNA was only correlated with sst2 in patients who were controlled with SRL. FLNA was not associated with tumor invasiveness.

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MeSH Terms

Acromegaly
Adenoma
Adolescent
Adult
Aged
Antineoplastic agents
Cell Membrane
Cell Nucleus
Cytoplasm
Female
Filamins
Growth hormone-secreting pituitary adenoma
Humans
Male
Middle aged
Octreotide
Peptides, cyclic
Receptors, dopamine D2
Receptors, somatostatin
Somatostatin
Tumor burden
Young adult

DeCS Terms

Acromegalia
Adenoma hipofisario secretor de hormona del crecimiento
Antineoplásicos
Carga tumoral
Citoplasma
Filaminas
Membrana celular
Núcleo celular
Octreótido
Persona de mediana edad
Péptidos cíclicos
Receptores de dopamina D2
Receptores de somatostatina

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