This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent studies from our laboratory have demonstrated high levels of nicotinic receptors (nAChR) and muscarinic receptors (mAChR) in airway epithelial cells, pulmonary neuroendocrine cells (PNEC) and pulmonary type II cells. Since these cell types are related to the origin of squamous cell carcinomas (SCC), small cell lung carcinomas (SCLC), bronchoalveolar carcinomas (BAC), respectively, it is highly likely that these carcinomas will also express nAChR and mAChR. Since the nAChR is a ligand-gated ion channel that leads to increased intracellular cellular calcium, activation of these receptors typically stimulates cellular growth. Adding further significance is the recent observation from our laboratory that these cell types also make acetylcholine, the ligand for both nAChR and mAChR. This suggests an autocrine loop in which lung cancers secrete acetylcholine to stimulate their own growth. While the expression of nicotinic receptors in SCLC has been previously studied and nicotine has been clearly shown to stimulate growth of SCLC, our observation that SCLC may make acetylcholine and hence modulate their own growth is a new and exciting observation. Hence, how exogenous ligand (i.e., nicotine from smoking) then interacts with the growth promoting effects of endogenous ligand (acetylcholine) becomes a very important question. Thus the purpose of this study is to determine if SCLC, SCC and BAC express acetylcholine, nAChR and mAChR and to then determine the potential for antagonists of cholinergic signaling to provide new approaches to blocking the growth and development of lung cancer.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000163-50
Application #
7958416
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2009-08-04
Project End
2010-04-30
Budget Start
2009-08-04
Budget End
2010-04-30
Support Year
50
Fiscal Year
2009
Total Cost
$80,343
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
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