Document Detail


The effect of PTEN on serotonin synthesis and secretion from the carcinoid cell line BON.
MedLine Citation:
PMID:  21508359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Carcinoid tumors are associated with the carcinoid syndrome, a set of symptoms resulting from the peptide and amine products, including serotonin, secreted from the cancer cells. The purpose of this study was to investigate the relationship between the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) inhibitor PTEN (phosphatase and tensin homolog deleted on chromosome ten) and serotonin synthesis and secretion in the carcinoid cancer cell line BON.
MATERIALS AND METHODS: PTEN was inhibited by pharmacological and molecular approaches, and the resultant secretion of serotonin and expression of tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, was assessed.
RESULTS: Inhibition of PTEN in vitro, with concomitant increased Akt signaling, resulted in decreased secretion of serotonin, as well as decreased serotonin synthesis, as confirmed by reduced expression of TPH1. Inhibition of PTEN in BON cells in an animal model resulted in decreased serum serotonin.
CONCLUSION: By inhibiting signaling through Akt, PTEN indirectly promotes serotonin synthesis and secretion.
Authors:
Scott R Silva; Yekaterina Y Zaytseva; Lindsey N Jackson; Eun Y Lee; Heidi L Weiss; Kanika A Bowen; Courtney M Townsend; B Mark Evers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Anticancer research     Volume:  31     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-21     Completed Date:  2011-07-26     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1153-60     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Carcinoid Tumor / drug therapy*,  metabolism,  pathology
Enzyme-Linked Immunosorbent Assay
Female
Immunoenzyme Techniques
Liver Neoplasms / drug therapy*,  metabolism,  secondary
Mice
Mice, Nude
PTEN Phosphohydrolase / antagonists & inhibitors,  pharmacology*
Phosphatidylinositol 3-Kinases / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
RNA, Small Interfering / genetics
Serotonin / metabolism*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
R01 CA104748/CA/NCI NIH HHS; R01 CA104748/CA/NCI NIH HHS; R01 CA104748-05/CA/NCI NIH HHS; R01 DK048498/DK/NIDDK NIH HHS; R01 DK048498-17/DK/NIDDK NIH HHS; R01 DK48489/DK/NIDDK NIH HHS; R37 AG010885/AG/NIA NIH HHS; R37 AG010885-20/AG/NIA NIH HHS; R37 AG10885/AG/NIA NIH HHS; T32 DK007639/DK/NIDDK NIH HHS; T32 DK007639-16/DK/NIDDK NIH HHS; T32DK07639/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; 333DO1RDJY/Serotonin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.1.3.48/PTEN protein, human; EC 3.1.3.67/PTEN Phosphohydrolase
Comments/Corrections

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