scholarly journals Resistance to octreotide LAR in acromegalic patients with high SSTR2 expression: analysis of AIP expression

2012 ◽  
Vol 56 (8) ◽  
pp. 501-506 ◽  
Author(s):  
Leandro Kasuki ◽  
Leandro M. Colli ◽  
Paula C. L. Elias ◽  
Margaret de Castro ◽  
Mônica R. Gadelha
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Molecular Data ◽  
Curative Surgery ◽  
Interacting Protein ◽  
Octreotide Lar ◽  
Expression Levels ◽  
Aryl Hydrocarbon

We present here the clinical and molecular data of two patients with acromegaly treated with octreotide LAR after non-curative surgery, and who presented different responses to therapy. Somatostatin receptor type 2 and 5 (SSTR2 and SSTR5), and aryl hydrocarbon receptor-interacting protein (AIP) expression levels were analyzed by qPCR. In both cases, high SSTR2 and low SSTR5 expression levels were detected; however, only one of the patients achieved disease control after octreotide LAR therapy. When we analyzed AIP expression levels of both cases, the patient whose disease was controlled after therapy exhibited AIP expression levels that were two times higher than the patient whose disease was still active. These two cases illustrate that, although the currently available somatostatin analogs bind preferentially to SSTR2, some patients are not responsive to therapy despite high expression of this receptor. This difference could be explained by differences in post-receptor signaling pathways, including the recently described involvement of AIP. Arq Bras Endocrinol Metab. 2012;56(8):501-6

scholarly journals AIP and the somatostatin system in pituitary tumours

2017 ◽  
Vol 235 (3) ◽  
pp. R101-R116 ◽  
Author(s):  
Alejandro Ibáñez-Costa ◽  
Márta Korbonits
Keyword(s):  
Zinc Finger Protein ◽  
Tumour Size ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Analogues ◽  
Pharmacological Therapy ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Classic somatostatin analogues aimed at somatostatin receptor type 2, such as octreotide and lanreotide, represent the mainstay of medical treatment for acromegaly. These agents have the potential to decrease hormone secretion and reduce tumour size. Patients with a germline mutation in the aryl hydrocarbon receptor-interacting protein gene, AIP, develop young-onset acromegaly, poorly responsive to pharmacological therapy. In this review, we summarise the most recent studies on AIP-related pituitary adenomas, paying special attention to the causes of somatostatin resistance; the somatostatin receptor profile including type 2, type 5 and truncated variants; the role of G proteins in this pathology; the use of first and second generation somatostatin analogues; and the role of ZAC1, a zinc-finger protein with expression linked to AIP in somatotrophinoma models and acting as a key mediator of octreotide response.

scholarly journals Octreotide promotes apoptosis in human somatotroph tumor cells by activating somatostatin receptor type 2

2006 ◽  
Vol 13 (3) ◽  
pp. 955-962 ◽  
Author(s):  
E Ferrante ◽  
C Pellegrini ◽  
S Bondioni ◽  
E Peverelli ◽  
M Locatelli ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Cultured Cells ◽  
Somatostatin Receptor ◽  
Hormone Secretion ◽  
Somatostatin Analogs ◽  
Receptor Type ◽  
Apoptotic Activity ◽  
Long Acting ◽  
Induced Apoptosis

Somatostatin analogs currently used in the treatment of acromegaly and other neuroendocrine tumors inhibit hormone secretion and cell proliferation by binding to somatostatin receptor type (SST) 2 and 5. The antiproliferative pathways coupled to these receptors have been only partially characterized. The aim of this study was to evaluate the effect of octreotide and super selective SST2 (BIM23120) and SST5 (BIM23206) analogs on apoptotic activity and apoptotic gene expression in human somatotroph tumor cells. Eight somatotroph tumors expressing similar levels of SST2 and SST5 evaluated by real-time PCR and western blot analyses were included in the study. In cultured cells obtained from these tumors, octreotide induced a dose-dependent increase of caspase-3 activity (160 ± 20% vs basal at 10 nM) and cleaved cytokeratin 18 levels (172 ± 25% vs basal) at concentrations higher than 0.1 nM. This effect was due to SST2 activation since BIM23120 elicited comparable responses, while BIM23206 was ineffective. BIM23120-stimulated apoptosis was dependent on phosphatases, since it was abrogated by the inhibitor orthovanadate, and independent from the induction of apoptosis-related genes, such as p53, p63, p73, Bcl-2, Bax, BID, BIK, TNFSF8, and FADD. In somatotroph tumors, both BIM23120 and BIM2306 caused growth arrest as indicated by the increase in p27 and decrease in cyclin D1 expression. In conclusion, the present study showed that octreotide-induced apoptosis in human somatotroph tumor cells by activating SST2. This effect, together with the cytostatic action exerted by both SST2 and SST5 analogs, might account for the tumor shrinkage observed in acromegalic patients treated with long-acting somatostatin analogs.

scholarly journals Mutation analysis of aryl hydrocarbon receptor interacting protein (AIP) gene in colorectal, breast, and prostate cancers

2007 ◽  
Vol 96 (2) ◽  
pp. 352-356 ◽  
Author(s):  
M Georgitsi ◽  
A Karhu ◽  
R Winqvist ◽  
T Visakorpi ◽  
K Waltering ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutation Analysis ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Prostate Cancers ◽  
Aip Gene
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