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.
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Acknowledgements
We thank Dr Marjo Simonen (Novartis Pharma AG, Senior Scientific Expert Laboratory in Molecular and Cellular Biology) for critically reading the manuscript and helpful discussions, Chantal Huber for excellent technical assistance and Roland Schöb for graphical assistance. Special thanks to Dr Burkhardt Seifert (Department of Biostatistics, ISPM, University Zurich) for exceptional assistance in statistical analyses.
This study was supported by the Swiss National Science Foundation (Grant No. 31-63633).
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Oertle, T., Merkler, D. & Schwab, M. Do cancer cells die because of Nogo-B?. Oncogene 22, 1390–1399 (2003). https://doi.org/10.1038/sj.onc.1206278
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DOI: https://doi.org/10.1038/sj.onc.1206278