Interferon-mediated activation of the STAT signaling pathway in a human carcinoid tumor

Shan Wang, Stephen K. Tyring, Courtney M. Townsend, B. Mark Evers

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Growth inhibition of human cancers (e.g., endocrine tumors) by interferons (IFNs) has been demonstrated, but the exact cellular mechanisms remain largely undefined. IFNs and other cytokines can activate novel Stat (Signal transducers and activators of transcription) proteins, which translocate to the nucleus to activate target genes. The purpose of this study was to determine the effect of IFN-α and IFN-γ on the Stat pathway using a unique human pancreatic carcinoid tumor, BON, established in our laboratory. Methods: BON cells were treated with IFN-α (500 U/mL) or IFN-γ (500 U/mL); nuclear protein was extracted at selected intervals. Steady state levels of Stat proteins 1, 3, and 5 were measured by Western blot; protein binding was assessed by electrophoretic mobility shift assay (EMSA) using probes containing either the Stat1/Stat3 or Stat5 binding sites. Results: Treatment with IFN-α increased predominantly Stat3 and Stat5 protein levels and binding activities. IFN-γ increased Stat1, 3, and 5 protein levels, with maximal elevations occurring at 24 to 48 hours after addition; Stat3 and 5 binding activities were also increased. Conclusions: We have shown that both IFN-α and IFN-γ can induce Stat protein binding (particularly Stat3 and Stat5) to their cognate DNA consensus sites and increase Stat protein steady state levels in BON cells. Delineating the signaling pathways altered by IFN treatment will provide a better understanding of downstream gene targets and mechanisms for IFN-mediated growth inhibition of endocrine tumors.

Original languageEnglish (US)
Pages (from-to)642-649
Number of pages8
JournalAnnals of surgical oncology
Volume5
Issue number7
DOIs
StatePublished - Jan 1 1998

Keywords

  • Endocrine tumors
  • Interferon
  • Signal transduction pathways
  • Stat proteins

ASJC Scopus subject areas

  • Surgery
  • Oncology

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