Telomerase activity in peripheral blood mononuclear cells after whole body irradiation

Neuhof, Dirk; Bischof, Marc; Debus, Jürgen; Weber, Klaus-Josef

doi:10.3892/or.17.4.865

Cited by 4 publications

(3 citation statements)

References 18 publications

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“…Similar results were reported by Finnon et al (24), albeit in mouse cells, and by Leteurtre et al in AML-driven cell line (29). In contrast, an up-regulation of TA after irradiation was reported in peripheral blood mononuclear cells after mitogen stimulation and in hematopoietic cell lines (30). Interestingly, the group of Xing et al found that lymphocytes from normal controls did not activate telomerase after ex vivo irradiation, whereas lymphocytes isolated from patients with bladder and lung cancers exhibited telomerase activation (17).…”

Section: Discussionsupporting

confidence: 67%

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Ram

Uziel²,

Eldan³

et al. 2009

Clinical Cancer Research

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Purpose:Telomerase is considered currently as a hallmark of cancer, and its inhibition is expected to become an important anticancer modality. In contrast to abundant data concerning the effect of cytotoxic drugs on telomerase activity (TA), there is scant information on the effect of radiation on telomerase.The mechanism of telomerase regulation by irradiation has never been evaluated in detail. In the present study, we investigated the effect of radiation onTA and its regulation in cancer cells. Experimental Design:The effect of various radiation doses onTA in several malignant and nonmalignant cell lines was evaluated. All malignant cells exhibited similar telomerase response to radiation and its regulation was assessed at transcriptional and post-translational levels in K562 cells. Next step was the evaluation of the upstream signaling pathways leading to changes inTA using kinetics and specific inhibitors. Results: Radiation up-regulated TA in dose-dependent manner only in cancer cells. Telomerase was activated by phosphorylation by Akt and by cytoplasmic-nuclear shift. Transcriptional processes were not involved inTA. This telomerase regulation is mediated by Ras/phosphatidylinositol 3-kinase/Akt pathway. The canonical membrane effectors of irradiation (epidermal growth factor receptor, insulin-like growth factor-I receptor, and Ca 2+ influx) were not involved in this process. Conclusions: Radiation up-regulates telomerase activity specifically in cancer cells. This study adds to accumulating evidence pointing to post-translational level as important mode of telomerase regulation. Telomerase activation due to radiation may be detrimental in treatment of cancer. Data described in this study may add to future interventions aiming at inhibition of telomerase activation during irradiation.

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Section: Discussionsupporting

confidence: 67%

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Ram

Uziel²,

Eldan³

et al. 2009

Clinical Cancer Research

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“…Telomerase is known to be a ribonucleoprotein in human cells that exhibits reverse transcriptase activity ( 11 ). Telomerase contains an RNA component to provide a template for the synthesis of repeated telomeric sequences.…”

Section: Introductionmentioning

confidence: 99%

Methylation of CDKN2B CpG islands is associated with upregulated telomerase activity in children with acute lymphoblastic leukemia

Hu¹,

Chen²,

Liu³

et al. 2017

Oncology Letters

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The aim of the present study was to investigate the association between methylation of cyclin-dependent kinase inhibitor 2B (CDKN2B) CpG islands and telomerase activity in children with acute lymphoblastic leukemia (ALL). A total of 72 children with ALL and 12 children with immune thrombocytopenia (ITP) were subjected to bone marrow aspiration and methylation-specific polymerase chain reaction analysis, and modified telomeric repeat amplification protocol assay analyses, to evaluate CDKN2B methylation and telomerase activity, respectively. The results of the present study demonstrated that, of these 72 children with ALL, 31 exhibited CDKN2B methylation at diagnosis (43.1%), whereas 41 exhibited no CDKN2B methylation (36.9%). However, no CDKN2B methylation was detected in the ITP controls. Furthermore, the mean level of telomerase activity was 39.52±39.33 total product generated (TPG) units in children with ALL, which was significantly increased compared with 2.49±2.27 TPG units in the ITP controls (P=0.002). The mean levels of telomerase were 49.09±44.43 and 29.99±32.43 TPG units in children with ALL with and without CDKN2B methylation, respectively (P=0.041), therefore children with ALL exhibited significantly increased levels of telomerase. The increased telomerase activity was significantly associated with increased risk of childhood ALL (P=0.023). A total of 22/31 children with ALL with methylated CDKN2B (71.0%) and 17/41 children with ALL with unmethylated CDKN2B (41.46%) exhibited increased telomerase activity (>15 TPG units). The results of the present study suggest that hypermethylation of CDKN2B CpG islands and hyperactivity of telomerase are common events in childhood ALL, and hypermethylation of CDKN2B CpG islands was significantly associated with upregulated telomerase activity (P=0.013).

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“…Currently used techniques include the isolation of cancer cells from within the blood, magnetic bead separation (2)(3)(4)(5) and density-gradient centrifugation (6)(7)(8)(9); however, these are subject to problems associated with cost and operability. With regard to clinical applications, great demands are placed on devices that can be sterilized.…”

Section: Introductionmentioning

confidence: 99%

A nylon net filter coated with ethanolamine groups traps micrometastatic cancer cells with high specificity

Noda

Higuchi²

2008

Mol Med Rep

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Abstract. Techniques for cancer cell separation and retrieval from peripheral blood are not only used to prevent cancer metastasis, but also to understand its underlying mechanisms. We developed a surface-modified membrane with high specificity for cancer cells. Ethanolamine groups were introduced to the surface of the nylon net filter, and human colon cancer cell line Colo201 cells were suspended in peripheral blood derived from healthy volunteers. Subsequently, these blood samples were transmitted through 20 surface-modified nylon filters. The number of cancer and blood cells in the blood samples was calculated using flow cytometry before and after filtering. Nylon net filters coated with ethanolamine groups trapped approximately 90% of the Colo201 cells, while unmodified nylon net filters were unable to trap them. On the other hand, no significant differences were observed in the filtration rate of hematocyte components between the unmodified nylon net filter and the nylon net filter coated with ethanolamine groups. These data indicate that nylon net filters coated with ethanolamine groups are able to trap Colo201 cells at a higher specificity than unmodified nylon net filters, effectively isolating and removing them from the blood, and suggest the potential benefits of the prevention of metastasis, cancer assessment and examination technologies as essential pre-treatment strategies. IntroductionThe prevention of metastasis is the single most important aim of cancer therapy. Metastasis of the primary cancer begins when cancer cells migrate from the primary cancer via the peripheral circulation and are transported to the affected organ (1). Consequently, techniques for cancer cell separation and retrieval from peripheral blood are used not only to prevent cancer metastasis, but also to understand its underlying mechanisms. These techniques have various potential applications, such as in the clinical assessment of cancer.Currently used techniques include the isolation of cancer cells from within the blood, magnetic bead separation (2-5) and density-gradient centrifugation (6-9); however, these are subject to problems associated with cost and operability. With regard to clinical applications, great demands are placed on devices that can be sterilized. Sterilization techniques following cancer cell isolation are complex; returning blood to the body is not ideal from an infection prevention standpoint. As a result, cancer cell isolation from blood using existing technology should primarily be used for clinical assessment (10). However, we believe that removing cancer cells from blood and then returning the blood back to a patient can lead to the effective prevention of cancer metastasis. Consequently, it is necessary to develop a low-cost polymer membrane that can be used for straightforward cellular separation. To ensure that high-polymer materials can easily be sterilized, a high level of safety must be assured. Moreover, to ensure easy access to a low-cost high-volume supply, a highly convenient disposable medi...

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Telomerase activity in peripheral blood mononuclear cells after whole body irradiation

Cited by 4 publications

References 18 publications

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Methylation of CDKN2B CpG islands is associated with upregulated telomerase activity in children with acute lymphoblastic leukemia

A nylon net filter coated with ethanolamine groups traps micrometastatic cancer cells with high specificity

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