Cyclin K and cyclin D1b are oncogenic in myeloma cells. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Molecular Cancer Année : 2010

Cyclin K and cyclin D1b are oncogenic in myeloma cells.

Véronique Marsaud
  • Fonction : Auteur
Guergana Tchakarska
  • Fonction : Auteur
Geoffroy Andrieux
  • Fonction : Auteur
  • PersonId : 884280
Doulaye Dembele
Bernard Jost
Jack-Michel Renoir
  • Fonction : Auteur
  • PersonId : 1086710
  • IdRef : 085539902
Brigitte Sola

Résumé

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.

Dates et versions

hal-00492316 , version 1 (15-06-2010)

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Véronique Marsaud, Guergana Tchakarska, Geoffroy Andrieux, Jian-Miao Liu, Doulaye Dembele, et al.. Cyclin K and cyclin D1b are oncogenic in myeloma cells.. Molecular Cancer, 2010, 9, pp.103. ⟨10.1186/1476-4598-9-103⟩. ⟨hal-00492316⟩
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