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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

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

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Carcinoid Tumor
Transforming Growth Factors
Serotonin
Serotonin Receptors
Phosphatidylinositols
Hydrolysis
Growth
Cyclic AMP
Acetylcholine
Assays
Signal transduction
Acetic Acid
Transforming Growth Factor beta
Tumors
Signal Transduction
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Cell Culture Techniques
Binding Sites
Cells

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Novel action of transforming growth factor β1 in functioning human pancreatic carcinoid cells. / Ishizuka, Jin; Beauchamp, R. Daniel; Sato, Kazuo; Townsend, Courtney; Thompson, James C.

In: Journal of Cellular Physiology, Vol. 156, No. 1, 07.1993, p. 112-118.

Research output: Contribution to journalArticle

Ishizuka, J, Beauchamp, RD, Sato, K, Townsend, C & Thompson, JC 1993, 'Novel action of transforming growth factor β1 in functioning human pancreatic carcinoid cells', Journal of Cellular Physiology, vol. 156, no. 1, pp. 112-118.
Ishizuka, Jin ; Beauchamp, R. Daniel ; Sato, Kazuo ; Townsend, Courtney ; Thompson, James C. / Novel action of transforming growth factor β1 in functioning human pancreatic carcinoid cells. In: Journal of Cellular Physiology. 1993 ; Vol. 156, No. 1. pp. 112-118.
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