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Nicotine induces the up‐regulation of alpha‐7‐nicotinic receptors (α7‐nAChRs) in human squamous carcinoma of the lung via transcriptional mechanisms
Author(s) -
Dasgupta Piyali,
Lau Jamie K.,
Brown Kathleen C.,
Luo Haitao,
Chen Yi Charlie
Publication year - 2012
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.26.1_supplement.479.2
Subject(s) - nicotine , nicotinic agonist , pharmacology , chemistry , luciferase , in vivo , acetylcholine receptor , nicotinic acetylcholine receptor , receptor , cancer research , biology , medicine , biochemistry , transfection , microbiology and biotechnology , gene
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. Nicotine‐induced up‐regulation of α7‐nAChR was dependent on α7‐nAChRs and the protein kinase C (PKC) pathway. The up‐regulation of α7‐nAChR upon nicotine treatment was confirmed in H520 tumors xenotransplanted on chicken chorioallantoic membranes (CAM). Real‐time PCR and luciferase assays showed that nicotine increased α7‐nAChR levels by transcriptional mechanisms in SCC‐L cells and CAM tumors. ChIP showed that nicotine induced the binding of GATA4 or GATA6 to Sp1 on the α7‐nAChR‐promoter, thereby increasing its levels in human SCC‐L. 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.