α7-Nicotinic Acetylcholine Receptors Affect Growth Regulation of Human Mesothelioma Cells: Role of Mitogen-Activated Protein Kinase Pathway

Sonya Trombino, Alfredo Cesario, Stefano Margaritora, PierLuigi Granone, Giovanni Motta, Carla Falugi, Patrizia Russo

Research output: Contribution to journalArticlepeer-review

Abstract

This study presents data suggesting that both human mesothelioma (cell lines and human mesothelioma biopsies) and human normal mesothelial cells express receptors for acetylcholine and that stimulation of these receptors by nicotine prompted cell growth via activation of nicotinic cholinergic receptors. Thus, these data demonstrate that: (a) human mesothelioma cells and human biopsies of mesothelioma as well as of normal pleural mesothelial cells express functionally α-7 nicotinic acethlycholine receptors, evaluated by α-bungarotoxin-FITC binding, receptor binding assay, Western blot, and reverse transcription-PCR; (b) choline acetyltransferase immunostaining is present in mesothelioma cells; (c) mesothelioma cell growth is modulated by the cholinergic system in which agonists (i.e., nicotine) has a proliferative effect, and antagonists (i.e., curare) has an inhibitory effect, evaluated by cell cloning, DNA synthesis and cell cycle; (d) nicotine induces Ca +2 influx, evaluated by [45Ca2+] uptake, and consequently activation of mitogen-activated protein kinase pathway (extracellular signal-regulated kinase and p90RSK phosphorylation), evaluated by Western blot; and (e) apoptosis mechanisms in mesothelioma cells are under the control of the cholinergic system (nicotine antiapoptotic via induction of nuclear factor-κB complexes and phosphorylation of Bad at Ser112; curare proapoptotic via G0-G1 arrest p21waf-1 dependent but p53 independent). The involvement of the nonneuronal cholinergic system in mesothelioma appears reasonable and open up new therapeutic strategies.

Original languageEnglish
Pages (from-to)135-145
Number of pages11
JournalCancer Research
Volume64
Issue number1
DOIs
Publication statusPublished - Jan 1 2004

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'α7-Nicotinic Acetylcholine Receptors Affect Growth Regulation of Human Mesothelioma Cells: Role of Mitogen-Activated Protein Kinase Pathway'. Together they form a unique fingerprint.

Cite this