Linked Life Data

19701709

Source:http://linkedlifedata.com/resource/pubmed/id/19701709

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-10-13
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1559-1166
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
391-401
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
PACAP induces signaling and stimulation of 5-hydroxytryptamine release and growth in neuroendocrine tumor cells.
pubmed:affiliation
Department of Medicine, University of California, CURE Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA. pgermano@ucla.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural