title: Alpha7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen-activated protein kinase pathway.
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 alpha-7 nicotinic acethlycholine receptors, evaluated by alpha-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 [(45)Ca(2+)] uptake, and consequently activation of mitogen-activated protein kinase pathway (extracellular signal-regulated kinase and p90(RSK) 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-kappaB complexes and phosphorylation of Bad at Ser(112); curare proapoptotic via G(0)-G(1) arrest p21(waf-1) dependent but p53 independent). The involvement of the nonneuronal cholinergic system in mesothelioma appears reasonable and open up new therapeutic strategies.
authors.affiliation: Department of Biology, University of Genoa, Genoa, Italy.
authors.forename: Sonya
authors.initials: S
authors.lastname: Trombino
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cesario
authors.forename: Stefano
authors.initials: S
authors.lastname: Margaritora
authors.forename: PierLuigi
authors.initials: P
authors.lastname: Granone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Motta
authors.forename: Carla
authors.initials: C
authors.lastname: Falugi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Russo
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001706:Biopsy; D002118:Calcium / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004261:DNA Replication; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008654:Mesothelioma / Q000473:pathology*; D010051:Ovarian Neoplasms; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D002118:Calcium