Document Detail


Cyclin K and cyclin D1b are oncogenic in myeloma cells.
MedLine Citation:
PMID:  20459741     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Aberrant expression of cyclin D1 is a common feature in multiple myeloma (MM) and always associated with mantle cell lymphoma (MCL). CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. Both isoforms are present in MM cell lines and primary cells but their relative role in the tumorigenic process is still elusive.
RESULTS: To test the tumorigenic potential of cyclin D1b in vivo, we generated cell clones derived from the non-CCND1 expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. Immunocompromised mice injected s.c. with LP-1K or LP-1D1b cells develop tumors at the site of injection. Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. Moreover, they impact differently cell functions. Cyclin K-expressing cells have lost their migration properties and display enhanced clonogenic capacities. Cyclin D1b promotes tumorigenesis through the stimulation of angiogenesis.
CONCLUSIONS: Our study indicates that cyclin D1b participates into MM pathogenesis via previously unrevealed actions.
Authors:
Véronique Marsaud; Guergana Tchakarska; Geoffroy Andrieux; Jian-Miao Liu; Doulaye Dembele; Bernard Jost; Joanna Wdzieczak-Bakala; Jack-Michel Renoir; Brigitte Sola
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-10
Journal Detail:
Title:  Molecular cancer     Volume:  9     ISSN:  1476-4598     ISO Abbreviation:  Mol. Cancer     Publication Date:  2010  
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-07-30     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101147698     Medline TA:  Mol Cancer     Country:  England    
Other Details:
Languages:  eng     Pagination:  103     Citation Subset:  IM    
Affiliation:
Biologie Moléculaire et Cellulaire de la Signalisation, EA 3919, IFR 146, Université de Caen, Caen, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle / physiology
Cell Line
Cell Movement / physiology
Cell Separation
Chick Embryo
Cyclin D1 / genetics,  metabolism*
Cyclins / genetics,  metabolism*
Female
Flow Cytometry
Humans
Immunoblotting
Immunohistochemistry
Mice
Mice, Nude
Multiple Myeloma / genetics,  metabolism*
Neovascularization, Pathologic / genetics,  metabolism
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/CCND1 protein, human; 0/CCNK protein, human; 0/Cyclins; 136601-57-5/Cyclin D1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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