Cyclin K and cyclin D1b are oncogenic in myeloma cells
Aberrant expression of cyclin D1 is a common feature of multiple myeloma (MM) pathology and always associated with mantle cell lymphoma (MCL) disease. CCND1 gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b.
While the long form cyclin D1a possesses a weak oncogenic capacity, the short cyclin D1b seems more potent. 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 MM LP-1 cell line, expressing either cyclin D1b or cyclin K, a structurally 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 a previously unrevealed actions.
Author: Veronique MarsaudGuergana TchakarskaGeoffroy AndrieuxJian-Miao LiuDoulaye DembeleBernard JostJoanna Wdzieczak-BakalaJack-Michel RenoirBrigitte Sola
Credits/Source: Molecular Cancer 2010, 9:103
Published on: 2010-05-10
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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