title: The effect of PTEN on serotonin synthesis and secretion from the carcinoid cell line BON.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  By inhibiting signaling through Akt, PTEN indirectly promotes serotonin synthesis and secretion.
authors.affiliation: Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Silva
authors.forename: Yekaterina Y
authors.initials: YY
authors.lastname: Zaytseva
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Jackson
authors.forename: Eun Y
authors.initials: EY
authors.lastname: Lee
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.forename: Kanika A
authors.initials: KA
authors.lastname: Bowen
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Townsend
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D034741:RNA, Small Interfering / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D034741:RNA, Small Interfering; D012701:Serotonin; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human