Relevance of cyclin D1b expression and CCND1 polymorphism in the pathogenesis of multiple myeloma and mantle cell lymphoma.
BACKGROUND
The CCND1 gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of a common A/G polymorphism. Cyclin D1a and b proteins differ in their C-terminus, a region involved in protein degradation and sub-cellular localization. Recent data have suggested that cyclin D1b could be a nuclear oncogene. The presence of cyclin D1b mRNA and protein has been studied in two hemopathies in which cyclin D1 could be present: multiple myeloma (MM) and mantle cell lymphoma (MCL). The A/G polymorphism of CCND1 has also been verified in a series of patients.


METHODS
The expression of cyclin D1 mRNA isoforms has been studied by real-time quantitative PCR; protein isoforms expression, localization and degradation by western blotting. The CCND1 polymorphism was analyzed after sequencing genomic DNA.


RESULTS
Cyclin D1 mRNA isoforms a and b were expressed in mantle cell lymphoma (MCL) and multiple myeloma (MM). Cyclin D1b proteins were present in MCL, rarely in MM. Importantly, both protein isoforms localized the nuclear and cytoplasmic compartments. They displayed the same short half-life. Thus, the two properties of cyclin D1b recognized as necessary for its transforming activity are missing in MCL. Moreover, CCND1 polymorphism at the exon/intron boundary had no influence on splicing regulation in MCL cells.


CONCLUSIONS
Our results support the notion that cyclin D1b is not crucial for the pathogenesis of MCL and MM.
Krieger
Sophie
S
Laboratoire de Biologie Moléculaire et Cellulaire de la Signalisation, EA 3919, Université de Caen, France. s.krieger@baclesse.fr
Gauduchon
Juliette
J
Roussel
Mikel
M
Troussard
Xavier
X
Sola
Brigitte
B
D045744:Cell Line, Tumor; D056741:Cyclin D; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D056741:Cyclin D; D016213:Cyclins; D012333:RNA, Messenger