title: Nicotinic acetylcholine receptor-mediated mechanisms in lung cancer.
abstract: Despite the known adverse health effects associated with tobacco use, over 45 million adults in the United States smoke. Cigarette smoking is the major etiologic factor associated with lung cancer. Cigarettes contain thousands of toxic chemicals, many of which are carcinogenic. Nicotine contributes directly to lung carcinogenesis through the activation of nicotinic acetylcholine receptors (nAChRs). nAChRs are ligand-gated ion channels, expressed in both normal and lung cancer cells, which mediate the proliferative, pro-survival, angiogenic, and metastatic effects of nicotine and its nitrosamine derivatives. The underlying molecular mechanisms involve increases in intracellular calcium levels and activation of cancer signal transduction pathways. In addition, acetylcholine (ACh) acts as an autocrine or paracrine growth factor in lung cancer. Other neurotransmitters and neuropeptides also activate similar growth loops. Recent genetic studies further support a role for nAChRs in the development of lung cancer. Several nAChR antagonists have been shown to inhibit lung cancer growth, suggesting that nAChRs may serve as valuable targets for biomarker-guided lung cancer interventions.
authors.affiliation: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry, University of Massachusetts Medical School, 303 Belmont St., Worcester, MA 01604, USA. Ma.Reina.Improgo@umassmed.edu
authors.forename: Ma Reina
authors.initials: MR
authors.lastname: Improgo
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Tapper
authors.forename: Paul D
authors.initials: PD
authors.lastname: Gardner
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009538:Nicotine / Q000633:toxicity; D018733:Nicotinic Antagonists / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009538:Nicotine; D002118:Calcium