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Nerve Growth Factor as a Mitogen for a Pancreatic Carcinoid Cell Line
Author(s) -
Bold Richard J.,
Ishizuka Jin,
Rajaraman Srinivasan,
PerezPolo J. Regino,
Townsend Courtney M.,
Thompson James C.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64062622.x
Subject(s) - nerve growth factor , tropomyosin receptor kinase a , neurotrophin , biology , medicine , endocrinology , paracrine signalling , receptor tyrosine kinase , low affinity nerve growth factor receptor , microbiology and biotechnology , autocrine signalling , growth factor , cell culture , receptor , signal transduction , genetics
Carcinoid tumors are a group of neuroendocrine neoplasms distributed widely throughout the body but most commonly occurring in the gut. These tumors retain many characteristics of their neural crest origin, including secretion of neuroactive peptides and responsiveness to neurotrophic substances. Nerve growth factor (NGF), a neurotrophic protein involved in maintenance and differentiation of peripheral sympathetic and sensory neurons, regulates growth of several neural tumor cells by inducing a differentiated phenotype and subsequent inhibition of cell growth rate. We examined the actions of NGF in a functioning human pancreatic carcinoid cell line (termed BON). NGF has no effect on the cytoarchitecture or constitutive secretion of bioamines in this carcinoid cell line. NGF, however, stimulates the in vitro cellular proliferation of BON cells. BON cells possess mRNA for the NGF receptors (p75 LNGFR and p140 trkA ) and membrane‐associated tyrosine kinase activity is increased in response to NGF. Both the mitogenic activity of NGF, as well as the receptor‐linked tyrosine kinase activity, can be abrogated in BON cells by the trkA inhibitor K‐252a and specific anti‐NGF antibody. Our studies demonstrate that NGF is a mitogen for this carcinoid cell line without effect on cellular phenotype or cytoarchitecture. NGF may play a role in the development and progression of human carcinoid tumors.