Document Detail

Phosphorylation of sst2 receptors in neuroendocrine tumors after octreotide treatment of patients.
MedLine Citation:
PMID:  22538189     Owner:  NLM     Status:  MEDLINE    
Somatostatin analogues, which are used to treat neuroendocrine tumors, target the high levels of somatostatin receptor subtype 2 (SSTR1; alias sst2) expressed in these cancers. However, some tumors are resistant to somatostatin analogues, and it is unknown whether the defect lies in sst2 activation or downstream signaling events. Because sst2 phosphorylation occurs rapidly after receptor activation, we examined whether sst2 is phosphorylated in neuroendocrine tumors. The sst2 receptor phosphorylation was evaluated by IHC and Western blot analysis with the new Ra-1124 antibody specific for the sst2 receptor phosphorylated at Ser341/343 in receptor-positive neuroendocrine tumors obtained from 10 octreotide-treated and 7 octreotide-naïve patients. The specificity, time course, and subcellular localization of sst2 receptor phosphorylation were examined in human embryo kinase-sst2 cell cultures by immunofluorescence and confocal microscopy. All seven octreotide-naïve tumors displayed exclusively nonphosphorylated cell surface sst2 expression. In contrast, 9 of the 10 octreotide-treated tumors contained phosphorylated sst2 that was predominantly internalized. Western blot analysis confirmed the IHC data. Octreotide treatment of human embryo kinase-sst2 cells in culture demonstrated that phosphorylated sst2 was localized at the plasma membrane after 10 seconds of stimulation and was subsequently internalized into endocytic vesicles. These data show, for the first time to our knowledge, that phosphorylated sst2 is present in most gastrointestinal neuroendocrine tumors from patients treated with octreotide but that a striking variability exists in the subcellular distribution of phosphorylated receptors among such tumors.
Beatrice Waser; Renzo Cescato; Qisheng Liu; Yachu J Kao; Meike Körner; Emanuel Christ; Agnes Schonbrunn; Jean Claude Reubi
Related Documents :
20860039 - The quinoxaline anti-tumor agent (r+)xk469 inhibits neuroblastoma tumor growth.
22776839 - Predictive value of immunohistochemical expression of claudin-1 in colonic carcinoma.
22747799 - Neonatal spiradenoma.
3682079 - The efficacy of chemotherapeutic agents against murine bladder metastasis.
22633289 - Neonatal soft tissue sarcomas.
22740829 - Decreased vision and junctional scotoma from pituicytoma.
17704359 - Functional vegf and vegf receptors are expressed in human medulloblastomas.
2032419 - Inhibition of lung colonization at two different steps in the metastatic sequence.
20144179 - Rare form of extraovarian peritoneal serous papillary carcinoma with solitary tumor in ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The American journal of pathology     Volume:  180     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-08-06     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1942-9     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Antineoplastic Agents, Hormonal / pharmacology*,  therapeutic use
Carcinoma, Neuroendocrine / drug therapy,  metabolism*,  surgery
Chemotherapy, Adjuvant
Microscopy, Confocal
Microscopy, Fluorescence
Neoplasm Proteins / drug effects,  metabolism
Octreotide / pharmacology*,  therapeutic use
Phosphorylation / drug effects
Receptors, Somatostatin / drug effects,  metabolism*
Grant Support
Reg. No./Substance:
0/Antineoplastic Agents, Hormonal; 0/Neoplasm Proteins; 0/Receptors, Somatostatin; 0/somatostatin receptor 2; 83150-76-9/Octreotide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Amplification of the STOML3, FREM2, and LHFP Genes Is Associated with Mesenchymal Differentiation in...
Next Document:  A Novel, Dual Role of CCN3 in Experimental Glomerulonephritis: Pro-Angiogenic and Antimesangioprolif...