Cyclin K and cyclin D1b are oncogenic in myeloma cells
| Autor: | Doulaye Dembélé, Jian-Miao Liu, Joanna Wdzieczak-Bakala, Guergana Tchakarska, Bernard Jost, Geoffroy Andrieux, Véronique Marsaud, Brigitte Sola, Jack-Michel Renoir |
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| Přispěvatelé: | Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Předmět: |
Cancer Research
Cyclin E Cyclin D Immunoblotting Cyclin A Cyclin B Mice Nude Cell Separation Chick Embryo [SDV.BC]Life Sciences [q-bio]/Cellular Biology lcsh:RC254-282 Cell Line Mice 03 medical and health sciences 0302 clinical medicine Cyclin D1 Cell Movement Cyclin-dependent kinase Cyclins Animals Humans Oligonucleotide Array Sequence Analysis 030304 developmental biology 0303 health sciences Neovascularization Pathologic biology Reverse Transcriptase Polymerase Chain Reaction Research Cell Cycle Cell cycle Flow Cytometry lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Immunohistochemistry Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Molecular Medicine Female Multiple Myeloma Cyclin A2 |
| Zdroj: | Molecular Cancer Molecular Cancer, BioMed Central, 2010, 9, pp.103. ⟨10.1186/1476-4598-9-103⟩ Molecular Cancer, Vol 9, Iss 1, p 103 (2010) |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/1476-4598-9-103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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