ArticleBritish journal of cancer2012
Differential downregulation of telomerase activity by bortezomib in multiple myeloma cells-multiple regulatory pathways in vitro and ex vivo.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Epigenetic Deregulation of Telomere-Related Genes in Newly Diagnosed Multiple Myeloma Patients.Cancers · 2021Article
- Review
- Ribosomopathies: New Therapeutic Perspectives.Cells · 2020Review
- The Effects of Proteasome Inhibitors on Telomerase Activity and Regulation in Multiple Myeloma Cells.International journal of molecular sciences · 2019Article
- Novel combination of tanshinone I and lenalidomide induces chemo-sensitivity in myeloma cells by modulating telomerase activity and expression of shelterin complex and its associated molecules.Molecular biology reports · 2018Article
- Inhibition of Transforming Growth Factor-β Activation Diminishes Tumor Progression and Osteolytic Bone Disease in Mouse Models of Multiple Myeloma.The American journal of pathology · 2016Article
- Bortezomib-mediated down-regulation of telomerase and disruption of telomere homeostasis contributes to apoptosis of malignant cells.Oncotarget · 2015Article
- The effect of Bortezomib and Rapamycin on Telomerase Activity in Mantle Cell Lymphoma.Translational oncology · 2014Article
- Drug resistance in multiple myeloma: latest findings and new concepts on molecular mechanisms.Oncotarget · 2013Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe importance of telomerase in multiple myeloma (MM) is well established; however, its response to bortezomib has not been addressed.
methodsThe effect of bortezomib on telomerase activity and cell proliferation was evaluated in four MM cell lines and in myeloma cells obtained from eight patients. The mechanism of telomerase regulation on epigenetic, transcriptional, and post-translational levels was further assessed in two selected cell lines: ARP-1 and CAG. Clinical data were correlated with the laboratory findings.
resultsBortezomib downregulated telomerase activity and decreased proliferation in all cell lines and cells obtained from patients, albeit in two different patterns of kinetics. ARP-1 cells demonstrated higher and earlier sensitivity than CAG cells due to differential phosphorylation of hTERT by PKCα. Methylation of hTERT promoter was not affected. Transcription of hTERT was similarly inhibited in both lines by decreased binding of SP-1 and not of C-Myc and NFκB. The ex vivo results confirmed the in vitro findings and suggested existence of clinical relevance.
conclusionBortezomib downregulates telomerase activity in MM cells both transcriptionally and post-translationally. MM cells, both in vitro and in patients, exhibit different sensitivity to the drug due to different post-translational response. The effect of bortezomib on telomerase activity may correlate with resistance to bortezomib in patients, suggesting its potential utility as a pre-treatment assessment.
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