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Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation.

Klapper W, Krams M, Qian W, Janssen D, Parwaresch R - Br. J. Cancer (2003)

Bottom Line: Surprisingly, the activity levels were the same in most of the lymphomas analysed as compared to reactive lymph nodes.We demonstrate here that the magnitude of telomerase upregulation does not necessarily reflect the requirement of telomere compensation caused by proliferation.We suggest that the upregulation of specific telomere-binding proteins like TRF2 may contribute to telomere maintenance in malignant lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hematopathology and Lymph Node Registry Kiel, Niemannsweg 11, 24105 Kiel, Germany. Wklapper@path.uni-kiel.de

ABSTRACT
Telomere maintenance is a prerequisite for immortalisation, and in most malignant cells is carried out by telomerase, an enzyme that synthesis new telomeric repeats on the chromosome ends. In normal or reactive tissues with a high regenerative capacity, telomerase is regulated according to the telomere loss that occurs during proliferation. To evaluate the interaction of proliferation and telomerase activity in malignant lymphomas, we quantified telomerase expression in different non-Hodgkin lymphomas in comparison to normal or reactive lymph nodes. Surprisingly, the activity levels were the same in most of the lymphomas analysed as compared to reactive lymph nodes. Significantly higher activity was detected only in Burkitt's lymphoma. Telomerase activity correlated well with hTERT and c-myc expression, but was independent of proliferation. To evaluate interactions of telomere-binding protein expression on telomerase expression in non-Hodgkin lymphoma, the mRNA levels of TRF1, TRF2, tankyrase and hPif1 were assessed by real-time RT-PCR. We demonstrate here that the magnitude of telomerase upregulation does not necessarily reflect the requirement of telomere compensation caused by proliferation. Telomerase regulation in non-Hodgkin lymphomas is therefore uncoupled from proliferative stimuli found in reactive lymphoid tissue. We suggest that the upregulation of specific telomere-binding proteins like TRF2 may contribute to telomere maintenance in malignant lymphoma.

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Related in: MedlinePlus

Telomere-binding protein expression detected by real-time RT–PCR using TaqMan assays. The expression is indicated relative to β-actin endogenous control: (A) TRF1 (one-way analysis of variance: P=0.433); (B) TRF2 (one-way analysis of variance: P=0.0239), (C) tankyrase (one-way analysis of variance: P=0.508), (D) hPif1 (one-way analysis of variance: P=0.0105).
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fig3: Telomere-binding protein expression detected by real-time RT–PCR using TaqMan assays. The expression is indicated relative to β-actin endogenous control: (A) TRF1 (one-way analysis of variance: P=0.433); (B) TRF2 (one-way analysis of variance: P=0.0239), (C) tankyrase (one-way analysis of variance: P=0.508), (D) hPif1 (one-way analysis of variance: P=0.0105).

Mentions: If telomerase activity is needed for telomere length maintenance in immortal cells, the requirement for such an activity should be higher, the more and faster the cell divisions are carried out. As no differences in telomerase activity and hTERT expression could be detected in benign lymph nodes, MCL, FL and DLBL, although high variations in the proliferative index were present, we speculated that other mechanisms might contribute to telomere maintenance in these lymphomas. A number of specific telomere-binding proteins have been characterised so far. Among these are negative regulators of telomere length such as TRF1 and TRF2 (Smogorzewska et al, 2000), as well as positive regulators like tankyrase (Smith and De Lange, 2000). The helicase hPif1 has been described as a telomerase inhibitor (Zhou et al, 2000). We studied the expression levels of TRF1, TRF2 tankyrase and hPif1 in B-cell NHL by TaqMan RT–PCR (Figure 3Figure 3


Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation.

Klapper W, Krams M, Qian W, Janssen D, Parwaresch R - Br. J. Cancer (2003)

Telomere-binding protein expression detected by real-time RT–PCR using TaqMan assays. The expression is indicated relative to β-actin endogenous control: (A) TRF1 (one-way analysis of variance: P=0.433); (B) TRF2 (one-way analysis of variance: P=0.0239), (C) tankyrase (one-way analysis of variance: P=0.508), (D) hPif1 (one-way analysis of variance: P=0.0105).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376911&req=5

fig3: Telomere-binding protein expression detected by real-time RT–PCR using TaqMan assays. The expression is indicated relative to β-actin endogenous control: (A) TRF1 (one-way analysis of variance: P=0.433); (B) TRF2 (one-way analysis of variance: P=0.0239), (C) tankyrase (one-way analysis of variance: P=0.508), (D) hPif1 (one-way analysis of variance: P=0.0105).
Mentions: If telomerase activity is needed for telomere length maintenance in immortal cells, the requirement for such an activity should be higher, the more and faster the cell divisions are carried out. As no differences in telomerase activity and hTERT expression could be detected in benign lymph nodes, MCL, FL and DLBL, although high variations in the proliferative index were present, we speculated that other mechanisms might contribute to telomere maintenance in these lymphomas. A number of specific telomere-binding proteins have been characterised so far. Among these are negative regulators of telomere length such as TRF1 and TRF2 (Smogorzewska et al, 2000), as well as positive regulators like tankyrase (Smith and De Lange, 2000). The helicase hPif1 has been described as a telomerase inhibitor (Zhou et al, 2000). We studied the expression levels of TRF1, TRF2 tankyrase and hPif1 in B-cell NHL by TaqMan RT–PCR (Figure 3Figure 3

Bottom Line: Surprisingly, the activity levels were the same in most of the lymphomas analysed as compared to reactive lymph nodes.We demonstrate here that the magnitude of telomerase upregulation does not necessarily reflect the requirement of telomere compensation caused by proliferation.We suggest that the upregulation of specific telomere-binding proteins like TRF2 may contribute to telomere maintenance in malignant lymphoma.

View Article: PubMed Central - PubMed

Affiliation: Institute of Hematopathology and Lymph Node Registry Kiel, Niemannsweg 11, 24105 Kiel, Germany. Wklapper@path.uni-kiel.de

ABSTRACT
Telomere maintenance is a prerequisite for immortalisation, and in most malignant cells is carried out by telomerase, an enzyme that synthesis new telomeric repeats on the chromosome ends. In normal or reactive tissues with a high regenerative capacity, telomerase is regulated according to the telomere loss that occurs during proliferation. To evaluate the interaction of proliferation and telomerase activity in malignant lymphomas, we quantified telomerase expression in different non-Hodgkin lymphomas in comparison to normal or reactive lymph nodes. Surprisingly, the activity levels were the same in most of the lymphomas analysed as compared to reactive lymph nodes. Significantly higher activity was detected only in Burkitt's lymphoma. Telomerase activity correlated well with hTERT and c-myc expression, but was independent of proliferation. To evaluate interactions of telomere-binding protein expression on telomerase expression in non-Hodgkin lymphoma, the mRNA levels of TRF1, TRF2, tankyrase and hPif1 were assessed by real-time RT-PCR. We demonstrate here that the magnitude of telomerase upregulation does not necessarily reflect the requirement of telomere compensation caused by proliferation. Telomerase regulation in non-Hodgkin lymphomas is therefore uncoupled from proliferative stimuli found in reactive lymphoid tissue. We suggest that the upregulation of specific telomere-binding proteins like TRF2 may contribute to telomere maintenance in malignant lymphoma.

Show MeSH
Related in: MedlinePlus