title: Loss of serum and glucocorticoid-regulated kinase 3 (SGK3) does not affect proliferation and survival of multiple myeloma cell lines.
abstract: Multiple myeloma (MM) is a generally fatal plasma cell cancer that often shows activation of the phosphoinositide 3-kinase/Akt (PI3K/Akt) pathway. Targeted pharmacologic therapies, however, have not yet progressed beyond the clinical trial stage, and given the complexity of the PI3K/Akt signalling system (e.g. multiple protein isoforms, diverse feedback regulation mechanisms, strong variability between patients) it is mandatory to characterise its ramifications in order to better guide informed decisions about the best therapeutic approaches. Here we explore whether serum and glucocorticoid-regulated kinase 3 (SGK3), a potential downstream effector of PI3K, plays a role in oncogenic signalling in MM cells--either in concert with or independent of Akt. SGK3 was expressed in all MM cell lines and in all primary MM samples tested. Four MM cell lines representing a broad range of intrinsic Akt activation (very strong: MM.1s, moderate: L 363 and JJN-3, absent: AMO-1) were chosen to test the effects of transient SGK3 knockdown alone and in combination with pharmacological inhibition of Akt, PI3K-p110α, or in the context of serum starvation. Although the electroporation protocol led to strong SGK3 depletion for at least 5 days its absence had no substantial effect on the activation status of potential downstream substrates, or on the survival, viability or proliferation of MM cells in all experimental contexts tested. We conclude that it is unlikely that SGK3 plays a significant role for oncogenic signalling in multiple myeloma.
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Oncology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hausmann
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Oncology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Brandt
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Oncology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Köchel
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Oncology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Ralf C
authors.initials: RC
authors.lastname: Bargou
authors.affiliation: Comprehensive Cancer Center Mainfranken, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Seggewiss-Bernhardt
authors.affiliation: Department of Internal Medicine II, Division of Hematology and Oncology, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stühmer
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D058534:Class I Phosphatidylinositol 3-Kinases; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C484760:PIK3CA protein, human; C403243:SGK3 protein, human; D000099184:Serum-Glucocorticoid Regulated Kinases
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