ArticleJournal of molecular neuroscience : MN2009
PACAP induces signaling and stimulation of 5-hydroxytryptamine release and growth in neuroendocrine tumor cells.
Article in Journal of molecular neuroscience : MN, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Crinophagy in Pancreatic Beta Cells: From Insulin Granule Turnover to Diabetes Pathogenesis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Molecular requirements for mammalian crinophagy highlight a key role for CaResearch square · 2025Article
- The G Protein-Coupled Receptor PAC1 Regulates Transactivation of the Receptor Tyrosine Kinase HER3.Journal of molecular neuroscience : MN · 2021Article
- Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and MigrationFrontiers in oncology · 2021Article
- PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner.Peptides · 2019Article
- Presence and Effects of Pituitary Adenylate Cyclase Activating Polypeptide Under Physiological and Pathological Conditions in the Stomach.Frontiers in endocrinology · 2018Review
- UTP - Gated Signaling Pathways of 5-HT Release from BON Cells as a Model of Human Enterochromaffin Cells.Frontiers in pharmacology · 2017Article
- Examination of PACAP-Like Immunoreactivity in Urogenital Tumor Samples.Journal of molecular neuroscience : MN · 2016Article
- Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer.Current opinion in endocrinology, diabetes, and obesity · 2016Review
- Illuminating somatostatin analog action at neuroendocrine tumor receptors.Trends in pharmacological sciences · 2013Review
- Purinergic autocrine regulation of mechanosensitivity and serotonin release in a human EC model: ATP-gated P2X3 channels in EC are downregulated in ulcerative colitis.Inflammatory bowel diseases · 2013Article
- Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor.Biochimica et biophysica acta · 2013Article
- Alternative Splicing of the Pituitary Adenylate Cyclase-Activating Polypeptide Receptor PAC1: Mechanisms of Fine Tuning of Brain Activity.Frontiers in endocrinology · 2013Article
- Pituitary adenylate cyclase-activating polypeptide causes tyrosine phosphorylation of the epidermal growth factor receptor in lung cancer cells.The Journal of pharmacology and experimental therapeutics · 2012Article
- Pituitary adenylate cyclase-activating polypeptide causes increased tyrosine phosphorylation of focal adhesion kinase and paxillin.Journal of molecular neuroscience : MN · 2012Article
- The effect of PTEN on serotonin synthesis and secretion from the carcinoid cell line BON.Anticancer research · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Neuroendocrine tumors, although rare, are currently diagnosed with increasing frequency, owing to improved imaging techniques and a greater clinical awareness of this condition. To date, BON is a very well established and characterized human pancreatic neuroendocrine tumor cell line used to study the signal transduction and genetic regulation of neuroendocrine tumors secretion and growth. The secretory activity of BON cells is known to release peptides, such as chromogranin A, neurotensin, and biogenic amines, as 5-HT, permitting an assessment of their biological activity. The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP), released from the enteric neurons in the gastrointestinal tract by binding to its high affinity receptor PAC1, has been previously shown to regulate the secretory activity and growth of the neuroendocrine-derived enterochromaffin-like cells in the stomach. This led us to speculate that PACAP might also play an important role in regulating the growth of human neuroendocrine tumors. Accordingly, in the current study, we have shown that BON cells express PAC1 receptors, which are rapidly internalized upon PACAP activation. Furthermore, PAC1 receptor activation, in BON cells, couple to intracellular Ca(2+) as well as cAMP responses and induce the release of intracellular 5-HT, activate mitogen activated protein kinases, and stimulate cellular growth. These data indicate that PACAP functionally can stimulate 5-HT release and promote the growth of the BON neuroendocrine tumor cell line. Therefore, PACAP and its receptors regulate neuroendocrine tumor secretory activity and growth in vivo, and this knowledge will permit the development of novel diagnostic and therapeutic targets for managing neuroendocrine tumors in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.