Relevance of cyclin D1b expression and CCND1polymorphism in the pathogenesis of multiple myeloma and mantle cell lymphoma

Krieger, Sophie; Gauduchon, Juliette; Roussel, Mikaël; Troussard, Xavier; Sola, Brigitte

doi:10.1186/1471-2407-6-238

Cited by 28 publications

(25 citation statements)

References 15 publications

(20 reference statements)

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“…At present, most human cancers that may be influenced by cyclin D1b protein activity have been identified largely through association with the G/A870 polymorphism [15]. However, many studies do not reach concordant results and increasing evidences have demonstrated that the presence of the G/A870 polymorphism is not a prerequisite for the expression of cyclin D1b [16,17]. On the other hand, the expression levels of cyclin D1 protein in lung cancer tissues have been analyzed mainly by immunohistochemical staining [2,10,18], and the data obtained showed that cyclin D1 expression is variable among tumors [11].…”

Section: Introductionmentioning

confidence: 99%

Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients

Li¹,

An²,

Chen³

et al. 2008

Human Pathology

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Section: Introductionmentioning

confidence: 99%

Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients

Li¹,

An²,

Chen³

et al. 2008

Human Pathology

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“…The suggestion that cytoplasmic sequestration regulates cyclin D1 activity in postmitotic neurons, neonatal cardiomyocytes and cancer cell lines is partly based on experiments that involved subcellular fractionation techniques [19,45,75,76]. Importantly, the fractionation of mantle cell lymphoma (MCL) and multiple myeloma (MM) cell lines suggests that cyclin D1b localizes to both the nucleus and cytoplasm [73]. At present, the significance of the observations made in studies using subcellular fractionation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention

2007

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Cyclin D1 is an important regulator of cell cycle progression and can function as a transcriptionl co-regulator. The overexpression of cyclin D1 has been linked to the development and progression of cancer. Deregulated cyclin D1 degradation appears to be responsible for the increased levels of cyclin D1 in several cancers. Recent findings have identified novel mechanisms involved in the regulation of cyclin D1 stability. A number of therapeutic agents have been shown to induce cyclin D1 degradation. The therapeutic ablation of cyclin D1 may be useful for the prevention and treatment of cancer. In this review, current knowledge on the regulation of cyclin D1 degradation is discussed. Novel insights into cyclin D1 degradation are also discussed in the context of ablative therapy. A number of unresolved questions regarding the regulation of cellular cyclin D1 levels are also addressed.

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“…Although cyclin D1 is overexpressed in MM cells, its relevance remains to be determined. Krieger et al 32 showed that cyclin D1a and b mRNA isoforms were both expressed in MM. However, the protein form of cyclin D1b was rarely expressed.…”

Section: P276-00 Is Active In An MM Xenograft Modelmentioning

confidence: 99%

Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma

et al. 2009

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Cyclin D dysregulation and overexpression is noted in the majority of multiple myeloma (MM) patients, suggesting its critical role in MM pathogenesis. Here, we sought to identify the effects of targeting cyclin D in MM. We first confirmed cyclin D mRNA overexpression in 42 of 64 (65%) patient plasma cells. Silencing cyclin D1 resulted in 450% apoptotic cell death suggesting its validity as a potential therapeutic target. We next evaluated P276-00, a clinical-grade small-molecule cyclindependent kinase inhibitor as a way to target the cyclins. P276-00 resulted in dose-dependent cytotoxicity in MM cells. Cell-cycle analysis confirmed either growth arrest or caspasedependent apoptosis; this was preceded by inhibition of Rb-1 phosphorylation with associated downregulation of a range of cyclins suggesting a regulatory role of P276-00 in cell-cycle progression through broad activity. Proliferative stimuli such as interleukin-6, insulin-like growth factor-1 and bone-marrow stromal cell adherence induced cyclins; P276-00 overcame these growth, survival and drug resistance signals. Because the cyclins are substrates of proteasome degradation, combination studies with bortezomib resulted in synergism. Finally, in vivo efficacy of P276-00 was confirmed in an MM xenograft model. These studies form the basis of an ongoing phase I study in the treatment of relapsed/refractory MM.

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Relevance of cyclin D1b expression and CCND1polymorphism in the pathogenesis of multiple myeloma and mantle cell lymphoma

Cited by 28 publications

References 15 publications

Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients

Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients

The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention

Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma

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