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Role of the acetylcholine signaling system in human non‐small cell lung cancers (405.3)
Author(s) -
Brown Kathleen,
Lau Jamie,
Thornhill Brent,
Perry Haley,
Stevenson Cathryn,
Rollyson William,
McNees Christopher,
Stover Cody,
Dasgupta Piyali
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.405.3
Subject(s) - choline acetyltransferase , nicotine , cholinergic , vesicular acetylcholine transporter , acetylcholine , nicotinic agonist , acetylcholine receptor , acetylcholinesterase , nicotinic acetylcholine receptor , cancer research , pharmacology , microbiology and biotechnology , chemistry , biology , receptor , endocrinology , neuroscience , biochemistry , enzyme
Clinical studies show that smoking correlates to 65% of non‐small cell lung cancer cases (NSCLC) in the United States. Nicotine, the major addictive component of cigarettes, accelerates proliferation of human NSCLCs via nicotinic acetylcholine receptors (nAChRs). However, the molecular pathways underlying the proliferative effects of nicotine are yet to be fully understood. The endogenous ligand for nAChRs in neuronal cells is acetylcholine (ACh). Here we show that human lung adenocarcinomas (LAC) produce ACh and contain all of the cholinergic system proteins, including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1), vesicular acetylcholine transporter (VAChT) and nAChRs. In addition, human LACs isolated from patients showed robust expression of ChAT and VAChT. Nicotine increased the production of ACh in human LAC cells. BrdU assays revealed that ACh acts as a growth factor for human LACs. Nicotine elevated the expression of VAChT and ChAT while downregulating the level of AChE in human NSCLCs. Our study shows that nicotine‐induced ACh production is one of the mechanisms by which nicotine promotes the proliferation of NSCLCs. Our data raise the possibility that that disruption of cholinergic signaling may have applications in the therapy of NSCLCs. Grant Funding Source : Supported by the Flight Attendant Medical Research Institute YCSA Grant and an NIH R15‐AREA Grant