Characterization of cyclin E expression in multiple myeloma and its functional role in seliciclib-induced apoptotic cell death.

PloS One
Liat Josefsberg Ben-YehoshuaArnon Nagler

Abstract

Multiple Myeloma (MM) is a lymphatic neoplasm characterized by clonal proliferation of malignant plasma cell that eventually develops resistance to chemotherapy. Drug resistance, differentiation block and increased survival of the MM tumor cells result from high genomic instability. Chromosomal translocations, the most common genomic alterations in MM, lead to dysregulation of cyclin D, a regulatory protein that governs the activation of key cell cycle regulator--cyclin dependent kinase (CDK). Genomic instability was reported to be affected by over expression of another CDK regulator--cyclin E (CCNE). This occurs early in tumorigenesis in various lymphatic malignancies including CLL, NHL and HL. We therefore sought to investigate the role of cyclin E in MM. CCNE1 expression was found to be heterogeneous in various MM cell lines (hMMCLs). Incubation of hMMCLs with seliciclib, a selective CDK-inhibitor, results in apoptosis which is accompanied by down regulation of MCL1 and p27. Ectopic over expression of CCNE1 resulted in reduced sensitivity of the MM tumor cells in comparison to the paternal cell line, whereas CCNE1 silencing with siRNA increased the cell sensitivity to seliciclib. Adhesion to FN of hMMCLs was prevented by sel...Continue Reading

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Citations

Sep 10, 2013·Current Opinion in Cell Biology·Céline Bruyère, Laurent Meijer
May 8, 2013·Expert Opinion on Investigational Drugs·Prithviraj BoseSteven Grant
Aug 13, 2013·Cancer Chemotherapy and Pharmacology·Ana Podolski-RenićMilica Pešić
Nov 23, 2017·Oncotarget·Anke MaesElke De Bruyne

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Methods Mentioned

BETA
reverse transcription PCR
flow cytometry
transfection
ubiquitination
xenograft
PCR
Assay
FACS

Software Mentioned

TINA
Olympus
Cell quest

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