title: Rituximab-induced early and late signaling have opposite effects on dexamethasone-induced apoptosis in human follicular lymphoma cells.
abstract: The addition of rituximab (RTX) to standard chemotherapy has improved the treatment of B-cell malignancies. We show here that RTX and dexamethasone (Dex) induced synergistic apoptosis in follicular lymphoma cell lines. However, apoptosis was delayed by RTX-induced early protective signaling. RTX-induced early signaling also decreased Dex-induced apoptosis and led to phosphorylation of ERK1/2, Bcl-2 (at serine 70) and phosphorylation/degradation of BimL/EL. All these events were prevented by the MEK inhibitor, UO126. Therefore, we suggest that RTX-induced ERK-mediated signaling events lead to protection from apoptosis during early signaling and that blocking of Bim and Bcl-2 phosphorylation might be used as a novel strategy for lymphoma treatment.
authors.affiliation: a Department of Clinical Microbiology , Institute of Clinical Medicine, University of Eastern Finland , Kuopio , Finland.|e Cancer Center of University of Eastern Finland , Kuopio , Finland.
authors.forename: Jemal
authors.initials: J
authors.lastname: Adem
authors.affiliation: a Department of Clinical Microbiology , Institute of Clinical Medicine, University of Eastern Finland , Kuopio , Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Ropponen
authors.affiliation: a Department of Clinical Microbiology , Institute of Clinical Medicine, University of Eastern Finland , Kuopio , Finland.
authors.forename: Jonna
authors.initials: J
authors.lastname: Eeva
authors.affiliation: b Fimlab Laboratories Oy, Tampere University Hospital , Tampere , Finland.|c Department of Medicine,University of Tampere , Tampere , Finland.
authors.forename: Mine
authors.initials: M
authors.lastname: Eray
authors.affiliation: a Department of Clinical Microbiology , Institute of Clinical Medicine, University of Eastern Finland , Kuopio , Finland.|d Eastern Finland Laboratory Centre (ISLAB) , Kuopio , Finland.|e Cancer Center of University of Eastern Finland , Kuopio , Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pelkonen
authors.affiliation: a Department of Clinical Microbiology , Institute of Clinical Medicine, University of Eastern Finland , Kuopio , Finland.
authors.forename: Ulla
authors.initials: U
authors.lastname: Nuutinen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008224:Lymphoma, Follicular / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000069283:Rituximab / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000069283:Rituximab; D003907:Dexamethasone; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Bim; Rituximab; apoptosis; dexamethasone; follicular lymphoma