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Long‐term exposure to nicotine upregulates the expression of α7‐nicotinic receptors by autoregulatory mechanisms in human squamous cell lung carcinoma
Author(s) -
Dasgupta Piyali,
Brown Kathleen C,
Luo Haitao,
Chen Yi C,
Lau Jamie K
Publication year - 2011
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.25.1_supplement.798.3
Nicotine, the active component of cigarettes, induces proliferation and angiogenesis in non‐small cell lung carcinomas (NSCLC) via the α7‐nicotinic acetylcholine receptor (nAChR). Our study examines the effect of long‐term nicotine exposure on α7‐nAChR expression in human NSCLC cells. Long term exposure to nicotine caused robust proliferation of human NSCLCs. The proliferative effects of nicotine were correlated to the upregulation of α7‐nAChR expression in a dose dependent manner, with the maximal effect observed between 100nM and 10μM. The treatment of human NSCLCs with 100nM nicotine produced a time‐dependent increase of α7‐nAChR expression starting from 4 to 12 days. Nicotine‐induced α7‐nAChR upregulation was reversed by the generalized nAChR‐antagonist mecamylamine and the protein kinase C inhibitor bisindolemeleiimide but was unaffected by chemical inhibitors of the Src or Akt pathway. Furthermore, α7‐nAChR antagonists (α‐bungarotoxin and MLA) reversed nicotine‐induced increases of α7‐nAChR expression. Our results suggest that nicotine stimulates the expression of α7‐nAChR in human NSCLCs by an autoregulatory mechanism involving protein kinase C.