Premium
Long‐term nicotine exposure elevates the expression of alpha7‐nicotinic receptors (α7‐nAChRs) in human squamous cell lung cancer cells via Sp1/GATA proteins (405.4)
Author(s) -
Dasgupta Piyali,
Brown Kathleen,
Perry Haley,
Lau Jamie,
Jones Dennie,
Pulliam Joseph,
Thornhill Brent,
Crabtree Clayton,
Chen Y
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.405.4
Subject(s) - nicotine , downregulation and upregulation , nicotinic agonist , pharmacology , receptor , chemistry , acetylcholine receptor , in vivo , nicotinic acetylcholine receptor , cancer research , medicine , biology , biochemistry , microbiology and biotechnology , gene
Smoking has a strong association with the development of squamous cell carcinomas of the lung (SCC‐L). Nicotine, the addictive component of cigarettes, promotes the proliferation of SCC‐Ls via the α7‐nicotinic acetylcholine receptors (α7‐nAChRs). We explore the effect of long‐term nicotine treatment on α7‐nAChR levels in SCC‐L in vitro and in vivo. Nicotine increased the expression of α7‐nAChR in a concentration‐dependent and time‐dependent manner in three human SCC‐L cell lines. We also found that the levels of α7‐nAChR in SCC‐Ls (isolated from heavy smokers) were greater than the levels in SCC‐L tumors isolated from moderate smokers. The upregulation of α7‐nAChR upon nicotine treatment was confirmed in chicken chorioallantoic membranes (CAM) models. Real‐time PCR and luciferase assays showed that nicotine increased α7‐nAChR levels by transcriptional mechanisms in SCC‐L cells. ChIP‐Re‐ChIP showed that nicotine induced the binding of GATA4 or GATA6 to Sp1 on the α7‐nAChR‐promoter, thereby increasing its levels in H520 SCC‐L cells. We also performed ChIP‐re‐ChIP assay in SCC‐L tumors isolated from patients with heavy to moderate smoking history and obtained similar results. Long‐term nicotine exposure could upregulate α7‐nAChRs on SCC‐L, thereby promoting its progression and metastasis. Our data is relevant to SCC‐L patients exposed to nicotine via second‐hand smoke or nicotine cessation devices. Grant Funding Source : Supported by the Flight Attendant Medical Research Institute YCSA Grant and an NIH R15‐AREA Grant