| Phosphorylation of sst2 receptors in neuroendocrine tumors after octreotide treatment of patients. | |
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MedLine Citation:
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PMID: 22538189 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Beatrice Waser; Renzo Cescato; Qisheng Liu; Yachu J Kao; Meike Körner; Emanuel Christ; Agnes Schonbrunn; Jean Claude Reubi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The American journal of pathology Volume: 180 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-27 Completed Date: 2012-08-06 Revised Date: 2013-05-02 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 1942-9 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Berne, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Hormonal
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pharmacology*,
therapeutic use Carcinoma, Neuroendocrine / drug therapy, metabolism*, surgery Chemotherapy, Adjuvant Humans Microscopy, Confocal Microscopy, Fluorescence Neoplasm Proteins / drug effects, metabolism Octreotide / pharmacology*, therapeutic use Phosphorylation / drug effects Receptors, Somatostatin / drug effects, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK032234/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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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
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