Role of α7-nicotinic acetylcholine receptor in human non-small cell lung cancer proliferation

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Errata

This article is corrected by:

  1. Errata: CORRIGENDUM Volume 42, Issue 1, 122, Article first published online: 14 January 2009
  2. Errata: ERRATUM Volume 42, Issue 4, 568, Article first published online: 29 June 2009

P. Russo, Lung Cancer Unit, National Cancer Research Institute, Largo Rosanna Benzi 10, I-16132 Genova, Italy. Tel.: +390105737255; Fax: +390105737571; E-mail: patrizia.russo@istge.it

Abstract

Abstract. Objectives: Lung cancer is the most common cause of cancer death in the world. Cigarette smoking represents the major risk factor. Nicotine, an active component of cigarettes, can induce cell proliferation, angiogenesis and apoptosis resistance. All these events are mediated through the nicotinic acetylcholine receptor (nAChR) expressed on lung cancer cells. We speculate that new insights into the pathophysiological roles of nAChR may lead to new therapeutic avenues to reduce non-small cell lung cancer (NSCLC) tumour growth. Materials and methods: Human samples of NSCLC, cell lines and mouse models were utilized in Western blotting, reverse transcriptase polymerase chain reaction and apoptosis studies. Results: Human NSCLC tissues expressed α7-nAChR. This expression was higher in smoking patients with squamous carcinomas than those with adenocarcinomas and in male smoking patients than in females. All the data support the hypothesis that major expression of α7-nAChR is related to major activation of the Rb–Raf-1/phospho-ERK/phospho-p90RSK pathway. α7-nAChR antagonists, via mitochondria associated apoptosis, inhibited proliferation of human NSCLC primary and established cells. Nicotine stimulates tumour growth in a murine model, A549 cells orthotopically grafted. The effects of nicotine were associated with increases in phospho-ERK in tumours. Proliferation effects of nicotine could be blocked by inhibition of α7-nAChR by the high affinity ligand α-cobratoxin. Conclusion: These results showed that α7-nAChR plays an important role in NSCLC cell growth and tumour progression as well as in cell death.

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