%0 Journal Article
%T Cyclin K and cyclin D1b are oncogenic in myeloma cells
%A V¨¦ronique Marsaud
%A Guergana Tchakarska
%A Geoffroy Andrieux
%A Jian-Miao Liu
%A Doulaye Dembele
%A Bernard Jost
%A Joanna Wdzieczak-Bakala
%A Jack-Michel Renoir
%A Brigitte Sola
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-103
%X 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.Our study indicates that cyclin D1b participates into MM pathogenesis via previously unrevealed actions.Cyclin D1 is a key actor for the development and progression of various cancers including hematological malignancies. The human CCND1 gene generates two mRNA species by alternative splicing [1]. The two corresponding proteins cyclin D1a and D1b differ only in the last 55 amino acids of the carboxy-terminus. Both isoforms possess the N-terminal domain, necessary for retinoblastoma protein (pRb) binding, the cyclin box, required for cyclin-dependent kinase (CDK) binding and activation and the central region, implicated in transcriptional regulation. The PEST sequence which controls protein turn-over and the threonine 286 (Thr286), the site of phosphorylation by glycogen synthase kinase-3¦Â which promotes the nuclear export of cyclin D1 and its degradation through the proteasome pathway [2,3], are present only in cyclin D1a. The oncogenic potential of cyclin D1 seems restricted to the isoform b as shown in vitro [4-6]. In transgenic mouse models, inhibition of cyclin D1 p
%U http://www.molecular-cancer.com/content/9/1/103