The effect of PTEN on serotonin synthesis and secretion from the carcinoid cell line BON

Anticancer Res. 2011 Apr;31(4):1153-60.

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.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoid Tumor / drug therapy*
  • Carcinoid Tumor / metabolism
  • Carcinoid Tumor / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoenzyme Techniques
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Mice
  • Mice, Nude
  • PTEN Phosphohydrolase / antagonists & inhibitors
  • PTEN Phosphohydrolase / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • RNA, Small Interfering / genetics
  • Serotonin / metabolism*
  • Tumor Cells, Cultured

Substances

  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Small Interfering
  • Serotonin
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human