Molecular evidence and clinical importance of β‐arrestins expression in patients with acromegaly

• Published in: Journal of cellular and molecular medicine Vol. 22; no. 4; pp. 2110 - 2116
• Main Authors: Coelho, Maria Caroline Alves, Vasquez, Marina Lipkin, Wildemberg, Luiz Eduardo, Vázquez‐Borrego, Mari C., Bitana, Luciana, Camacho, Aline Helen da Silva, Silva, Débora, Ogino, Liana Lumi, Ventura, Nina, Chimelli, Leila, Luque, Raul M., Kasuki, Leandro, Gadelha, Mônica R.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2018; John Wiley and Sons Inc
• Subjects: Acromegaly; Antigens; Arrestin; Dehydrogenases; Desensitization; Dopamine; Dopamine D2 receptors; dopamine receptor; Drug dosages; Endocytosis; Genes; Growth hormones; Immunohistochemistry; Invasiveness; Kinases; mRNA; Original; Patients; Proteins; Signal transduction; Somatostatin; somatostatin receptor ligands; somatostatin receptors; Surgery; Thermal cycling; Tumors; β‐arrestins; United States > US; acromegaly; β-arrestins; somatostatin receptor ligands; dopamine receptor; somatostatin receptors
• DOI: 10.1111/jcmm.13427
• ISSN: 1582-1838

β‐arrestins seem to have a role in endocytosis and desensitization of somatostatin receptor subtype 2 (sst2) and could be associated with the responsiveness to somatostatin receptor ligands (SRL) in patients with acromegaly. To investigate the in vivo correlation between β‐arrestins 1 and 2 with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the association of β‐arrestins with response to first‐generation SRL and invasiveness in somatotropinomas. β‐arrestins 1 and 2, sst2, sst5 and D2 mRNA expressions were evaluated by quantitative real‐time RT‐PCR on tumoral tissue of 96 patients. Moreover, sst2 and sst5 protein expressions were also evaluated in 40 somatotropinomas by immunohistochemistry. Response to SRL, defined as GH <1 μg/l and normal IGF‐I levels, was assessed in 40 patients. The Knosp‐Steiner criteria were used to define invasiveness. Median β‐arrestin 1, β‐arrestin 2, sst2, sst5 and D2 mRNA copy numbers were 478; 9375; 731; 156; and 3989, respectively. There was a positive correlation between β‐arrestins 1 and 2 (R = 0.444, P < 0.001). However, no correlation between β‐arrestins and sst2, sst5 (mRNA and protein levels) or D2 was found. No association was found between β‐arrestins expression and SRL responsiveness or tumour invasiveness. Although previous data suggest a putative correlation between β‐arrestins and sst2, our data clearly indicated that no association existed between β‐arrestins and sst2, sst5 or D2 expression, nor with response to SRL or tumour invasiveness. Therefore, further studies are required to clarify whether β‐arrestins have a role in the response to treatment with SRL in acromegaly.