title: Do cancer cells die because of Nogo-B?
abstract: Nogo-A is a potent neurite outgrowth inhibitory protein in vitro and is suggested to play a role in the lack of regeneration in the central nervous system of adult higher vertebrates. A shorter splice isoform, ASY/Nogo-B, has recently been reported to act as a proapoptotic protein, the loss of which would be typical for cancer cells. Here, we show that the osteosarcoma cell line SaOS-2 and the cell line CHO do express high levels of endogenous Nogo-B and that stable transfectants overexpressing high levels of Nogo-B do not differ significantly from the respective parental wild-type or control cell lines both in respect to cell proliferation and to spontaneous apoptosis or cell death induced by staurosporine and tunicamycin. The deletion of the second transmembrane domain of Nogo-B, which has been claimed to abolish its proapoptotic activity, leads to a shift of the protein from the ER to a cytoplasmic localization, suggesting that ER stress of highly overexpressed Nogo-B may lead to aversive cellular reactions under particular conditions. Our data do not support a function of Nogo-B as a physiological pro-apoptotic protein in certain types of cancer.
authors.affiliation: Brain Research Institute, University of Zurich and Department of Biology, ETH Zurich, Switzerland. oertlle@hio.unizh.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Oertle
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D016466:CHO Cells / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D000070798:Nogo Proteins; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D009185:Myelin Proteins; D009363:Neoplasm Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; D011993:Recombinant Fusion Proteins; C000603197:Rtn4 protein, rat; D014415:Tunicamycin; D019311:Staurosporine