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Loss of serum and glucocorticoid-regulated kinase 3 (SGK3) does not affect proliferation and survival of multiple myeloma cell lines
- Source :
- PLoS ONE, Vol 10, Iss 4, p e0122689 (2015), PLoS ONE
- Publication Year :
- 2015
-
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-p110\(\alpha\), 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.
- Subjects :
- Cell Survival
Class I Phosphatidylinositol 3-Kinases
lcsh:Medicine
Context (language use)
Protein Serine-Threonine Kinases
Biology
Phosphatidylinositol 3-Kinases
Cell Line, Tumor
Tumor Cells, Cultured
Humans
ddc:610
lcsh:Science
Protein kinase B
PI3K/AKT/mTOR pathway
Cell Proliferation
Multidisciplinary
Kinase
Cell growth
Effector
lcsh:R
Transfection
Cell biology
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Mutation
Cancer research
lcsh:Q
Signal transduction
Multiple Myeloma
Proto-Oncogene Proteins c-akt
Signal Transduction
Research Article
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, Vol 10, Iss 4, p e0122689 (2015), PLoS ONE
- Accession number :
- edsair.doi.dedup.....8d10068e7bd6ce4f5929e0f37188686b