Novel action of transforming growth factor β1 in functioning human pancreatic carcinoid cells

Jin Ishizuka, R. Daniel Beauchamp, Kazuo Sato, Courtney M. Townsend, James C. Thompson

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

We have shown recently that 5‐HT is an autocrine growth stimulatory factor for a cell line (BON) that is derived from a human pancreatic carcinoid tumor. This action is mediated by a 5‐HT receptor‐linked decrease of cyclic adenosine monophosphate (AMP) production, but not mediated by a 5‐HT receptor‐linked stimulation of phosphatidylinositol hydrolysis. The BON cells also express transforming growth factor betas (TGFβs) (1, 2, and 3) and release TGFβ into their medium. In this study, we examined the effects of TGFβ1 on the secretion of 5‐HT, on signal transduction pathways involved in 5‐HT secretion, and on growth of BON cells. TGFβ1 inhibited basal and acetylcholine‐stimulated release of 5‐HT, but did not inhibit isobutylmethylxanthine‐stimulated release of 5‐HT. TGFβ1 inhibited both basal and acetylcholine‐stimulated hydrolysis of phosphatidylinositol in a dose‐dependent manner, but did not affect cyclic AMP production. TGFβ1 inhibited growth of BON cells in culture; this effect was reversed by exogenously administered 5‐HT. Three different specific and saturable TGFβ1 binding sites were identified; binding assays performed after mild acid wash (0.1% acetic acid, pH 2.5) conditions uncovered TGFβ receptors that were apparently occupied by endogenously produced TGFβ species. Affinity cross‐linking assay showed that BON cells had three different TGFβ binding proteins. These results suggest that TGFβ1 can inhibit growth of BON cells by altering secretory responses of 5‐HT by means of receptor‐mediated inhibition of phosphatidylinositol hydrolysis. We conclude that growth of BON cells is regulated, at least in part, by the opposing receptor‐mediated autocrine actions of 5‐HT and TGFβ. © 1993 Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)112-118
Number of pages7
JournalJournal of Cellular Physiology
Volume156
Issue number1
DOIs
StatePublished - Jul 1993

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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