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

✍ Scribed by Jin Ishizuka; R. Daniel Beauchamp; Kazuo Sato; Courtney M. Townsend Jr.; James C. Thompson

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 788 KB
• Volume: 156
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041560116

✦ Synopsis

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 (TGFPs) (1, 2, and 3) and release TGFP into their medium. In this study, we examined the effects of TGFPl on the secretion of 5-HT, on signal transduction pathways involved in 5-HT secretion, and on growth of BON cells.

TGFPl inhibited basal and acetylcholine-stimulated release of 5-HT, but did not inhibit isobutylmethylxanthine-stimulated release of 5-HT. TGFPl inhibited both basal and acetylcholine-stimulated hydrolysis of phosphatidylinositol in a dosedependent manner, but did not affect cyclic AMP production. TGFPl inhibited growth of BON cells in culture; this effect was reversed by exogenously administered 5-HT. Three different specific and saturable TCFPl binding sites were identified; binding assays performed after mild acid wash (0.1 % acetic acid, p H 2.5) conditions uncovered TGFP receptors that were apparently occupied by endogenously produced TGFP species. Affinity cross-linking assay showed that BON cells had three different TGFP binding proteins. These results suggest that TGFPl 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 TGFP.