Cyclin K and cyclin D1b are oncogenic in myeloma cells.
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.
Marsaud
Véronique
V
Biologie Moléculaire et Cellulaire de la Signalisation, EA 3919, IFR 146, Université de Caen, Caen, France.
Tchakarska
Guergana
G
Andrieux
Geoffroy
G
Liu
Jian-Miao
JM
Dembele
Doulaye
D
Jost
Bernard
B
Wdzieczak-Bakala
Joanna
J
Renoir
Jack-Michel
JM
Sola
Brigitte
B
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002469:Cell Separation; D002642:Chick Embryo; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
C530104:CCND1 protein, human; C113028:CCNK protein, human; D016213:Cyclins; D019938:Cyclin D1
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