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Nicotine increases the expression of alpha7‐nicotinic receptors (alpha7‐nAChRs) in human squamous cell lung cancer cells via Sp1/GATA pathway
Author(s) -
Dasgupta Piyali,
Lau Jamie K,
Brown Kathleen C,
Luo Haitao,
Chen Yi C
Publication year - 2013
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.27.1_supplement.58.2
Subject(s) - nicotine , nicotinic agonist , acetylcholine receptor , pharmacology , in vivo , chemistry , luciferase , receptor , cell culture , nicotinic acetylcholine receptor , cancer research , medicine , biology , biochemistry , transfection , microbiology and biotechnology , genetics
Nicotine, the addictive component of cigarettes, promotes the proliferation of lung cancers via nicotinic acetylcholine receptors (nAChRs), specifically the α7‐nAChR subtype. We explore the effect of nicotine treatment on α7‐nAChR levels in squamous cell carcinomas of the lung (SCC‐L) in vitro and in vivo . Nicotine increased α7‐nAChR levels 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 SCC‐L tumors isolated from moderate smokers. Nicotine‐induced up‐regulation of α7‐nAChR was dependent on α7‐nAChRs. The up‐regulation 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 showed that nicotine induced the binding of GATA4 or GATA6 to Sp1 on the α7‐nAChR‐promoter, thereby increasing its levels in H520 human SCC‐L cells. We also performed ChIP assay in SCC‐L tumors isolated from patients with heavy to moderate smoking history and obtained similar results. Long‐term exposure to nicotine could up‐regulate α7‐nAChRs on SCC‐L, thereby promoting its progression and metastasis. Our data would also be relevant to SCC‐L patients exposed to nicotine via second‐hand smoke or nicotine patches/gums used to quit smoking.