Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue

Ann-Katrine Jakobsen, Kristina Lystlund Lauridsen, Evelyn Benuja Samuel, Joanna Proszek, Birgitta Ruth Knudsen, H. Hager, Magnus Stougaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Topoisomerase I (TOP1) regulates DNA topology during replication and transcription whereas tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in the repair of several types of DNA damages, including damages from defective TOP1 catalysis. TOP1 is the target of chemotherapeutic drugs of the camptothecin family (CPT). TDP1 has in cell line based assays been shown to counteract the effect of CPT. We have quantified the enzymatic activities of TOP1 and TDP1 in paired (tumor and adjacent non-tumor) samples from non-small cell lung cancer (NSCLC) patients and show that in NSCLC TOP1 and TDP1 activities are significantly upregulated in the tumor tissue. Furthermore, we found a positive correlation between the TDP1 activity and the tumor percentage (TOP1 activity did not correlate with the tumor percentage) as well as between the activities of TOP1 and TDP1 both within the tumor and the non-tumor group. That TDP1 activity was upregulated in all tumor samples and correlated with the tumor percentage suggest that it must play a highly important function in NSCLC. This could be to protect against TOP1 mediated DNA damage as the activity of TOP1 likewise was upregulated in the majority of tumor samples and correlated positively to the TDP1 activity. Regardless, the finding that the TOP1 and TDP1 activities are upregulated and correlate positively suggests that combinatorial treatment targeting both activities could be advantageous in NSCLC. (C) 2015 Elsevier Inc. All rights reserved.
OriginalsprogEngelsk
TidsskriftExperimental and Molecular Pathology
Vol/bind99
Udgave nummer1
Sider (fra-til)56-64
ISSN0014-4800
DOI
StatusUdgivet - 2015

Bibliografisk note

Aase og Ejnar Danielsens Fond; Kobmand Svend Hansen og hustru Ina Hansens Fond; Familien Hede Nielsens Fond; Marie & M. B. Richters Fond; Fabrikant Einar Willumsens Mindelegat; Kong Christian Den Tiendes Fond; Lykfeldts legat; Fhv. Dir. Leo Nielsen og Hustru Karen Margrethe Nielsens Legat for Laegevidenskabelig Grundforskning; Aage og Johanne Luis-Hansens Fond 0 25987486

Emneord

  • Lung cancer Topoisomerase I Tyrosyl-DNA phosphodiesterase 1 Biosensor Cryosection STRAND BREAK REPAIR SPINOCEREBELLAR ATAXIA COVALENT COMPLEXES AXONAL NEUROPATHY COLON-CANCER TDP1 DAMAGE CAMPTOTHECIN TOPOTECAN MUTATION

Citer dette

Jakobsen, Ann-Katrine ; Lauridsen, Kristina Lystlund ; Samuel, Evelyn Benuja ; Proszek, Joanna ; Knudsen, Birgitta Ruth ; Hager, H. ; Stougaard, Magnus. / Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue. I: Experimental and Molecular Pathology. 2015 ; Bind 99, Nr. 1. s. 56-64.
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title = "Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue",
abstract = "Topoisomerase I (TOP1) regulates DNA topology during replication and transcription whereas tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in the repair of several types of DNA damages, including damages from defective TOP1 catalysis. TOP1 is the target of chemotherapeutic drugs of the camptothecin family (CPT). TDP1 has in cell line based assays been shown to counteract the effect of CPT. We have quantified the enzymatic activities of TOP1 and TDP1 in paired (tumor and adjacent non-tumor) samples from non-small cell lung cancer (NSCLC) patients and show that in NSCLC TOP1 and TDP1 activities are significantly upregulated in the tumor tissue. Furthermore, we found a positive correlation between the TDP1 activity and the tumor percentage (TOP1 activity did not correlate with the tumor percentage) as well as between the activities of TOP1 and TDP1 both within the tumor and the non-tumor group. That TDP1 activity was upregulated in all tumor samples and correlated with the tumor percentage suggest that it must play a highly important function in NSCLC. This could be to protect against TOP1 mediated DNA damage as the activity of TOP1 likewise was upregulated in the majority of tumor samples and correlated positively to the TDP1 activity. Regardless, the finding that the TOP1 and TDP1 activities are upregulated and correlate positively suggests that combinatorial treatment targeting both activities could be advantageous in NSCLC. (C) 2015 Elsevier Inc. All rights reserved.",
keywords = "Lung cancer Topoisomerase I Tyrosyl-DNA phosphodiesterase 1 Biosensor Cryosection STRAND BREAK REPAIR SPINOCEREBELLAR ATAXIA COVALENT COMPLEXES AXONAL NEUROPATHY COLON-CANCER TDP1 DAMAGE CAMPTOTHECIN TOPOTECAN MUTATION",
author = "Ann-Katrine Jakobsen and Lauridsen, {Kristina Lystlund} and Samuel, {Evelyn Benuja} and Joanna Proszek and Knudsen, {Birgitta Ruth} and H. Hager and Magnus Stougaard",
note = "Aase og Ejnar Danielsens Fond; Kobmand Svend Hansen og hustru Ina Hansens Fond; Familien Hede Nielsens Fond; Marie & M. B. Richters Fond; Fabrikant Einar Willumsens Mindelegat; Kong Christian Den Tiendes Fond; Lykfeldts legat; Fhv. Dir. Leo Nielsen og Hustru Karen Margrethe Nielsens Legat for Laegevidenskabelig Grundforskning; Aage og Johanne Luis-Hansens Fond 0 25987486",
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Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue. / Jakobsen, Ann-Katrine; Lauridsen, Kristina Lystlund; Samuel, Evelyn Benuja; Proszek, Joanna; Knudsen, Birgitta Ruth; Hager, H.; Stougaard, Magnus.

I: Experimental and Molecular Pathology, Bind 99, Nr. 1, 2015, s. 56-64.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Correlation between topoisomerase I and tyrosyl-DNA phosphodiesterase 1 activities in non-small cell lung cancer tissue

AU - Jakobsen, Ann-Katrine

AU - Lauridsen, Kristina Lystlund

AU - Samuel, Evelyn Benuja

AU - Proszek, Joanna

AU - Knudsen, Birgitta Ruth

AU - Hager, H.

AU - Stougaard, Magnus

N1 - Aase og Ejnar Danielsens Fond; Kobmand Svend Hansen og hustru Ina Hansens Fond; Familien Hede Nielsens Fond; Marie & M. B. Richters Fond; Fabrikant Einar Willumsens Mindelegat; Kong Christian Den Tiendes Fond; Lykfeldts legat; Fhv. Dir. Leo Nielsen og Hustru Karen Margrethe Nielsens Legat for Laegevidenskabelig Grundforskning; Aage og Johanne Luis-Hansens Fond 0 25987486

PY - 2015

Y1 - 2015

N2 - Topoisomerase I (TOP1) regulates DNA topology during replication and transcription whereas tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in the repair of several types of DNA damages, including damages from defective TOP1 catalysis. TOP1 is the target of chemotherapeutic drugs of the camptothecin family (CPT). TDP1 has in cell line based assays been shown to counteract the effect of CPT. We have quantified the enzymatic activities of TOP1 and TDP1 in paired (tumor and adjacent non-tumor) samples from non-small cell lung cancer (NSCLC) patients and show that in NSCLC TOP1 and TDP1 activities are significantly upregulated in the tumor tissue. Furthermore, we found a positive correlation between the TDP1 activity and the tumor percentage (TOP1 activity did not correlate with the tumor percentage) as well as between the activities of TOP1 and TDP1 both within the tumor and the non-tumor group. That TDP1 activity was upregulated in all tumor samples and correlated with the tumor percentage suggest that it must play a highly important function in NSCLC. This could be to protect against TOP1 mediated DNA damage as the activity of TOP1 likewise was upregulated in the majority of tumor samples and correlated positively to the TDP1 activity. Regardless, the finding that the TOP1 and TDP1 activities are upregulated and correlate positively suggests that combinatorial treatment targeting both activities could be advantageous in NSCLC. (C) 2015 Elsevier Inc. All rights reserved.

AB - Topoisomerase I (TOP1) regulates DNA topology during replication and transcription whereas tyrosyl-DNA phosphodiesterase 1 (TDP1) is involved in the repair of several types of DNA damages, including damages from defective TOP1 catalysis. TOP1 is the target of chemotherapeutic drugs of the camptothecin family (CPT). TDP1 has in cell line based assays been shown to counteract the effect of CPT. We have quantified the enzymatic activities of TOP1 and TDP1 in paired (tumor and adjacent non-tumor) samples from non-small cell lung cancer (NSCLC) patients and show that in NSCLC TOP1 and TDP1 activities are significantly upregulated in the tumor tissue. Furthermore, we found a positive correlation between the TDP1 activity and the tumor percentage (TOP1 activity did not correlate with the tumor percentage) as well as between the activities of TOP1 and TDP1 both within the tumor and the non-tumor group. That TDP1 activity was upregulated in all tumor samples and correlated with the tumor percentage suggest that it must play a highly important function in NSCLC. This could be to protect against TOP1 mediated DNA damage as the activity of TOP1 likewise was upregulated in the majority of tumor samples and correlated positively to the TDP1 activity. Regardless, the finding that the TOP1 and TDP1 activities are upregulated and correlate positively suggests that combinatorial treatment targeting both activities could be advantageous in NSCLC. (C) 2015 Elsevier Inc. All rights reserved.

KW - Lung cancer Topoisomerase I Tyrosyl-DNA phosphodiesterase 1 Biosensor Cryosection STRAND BREAK REPAIR SPINOCEREBELLAR ATAXIA COVALENT COMPLEXES AXONAL NEUROPATHY COLON-CANCER TDP1 DAMAGE CAMPTOTHECIN TOPOTECAN MUTATION

U2 - 10.1016/j.yexmp.2015.05.006

DO - 10.1016/j.yexmp.2015.05.006

M3 - Journal article

C2 - 25987486

VL - 99

SP - 56

EP - 64

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

SN - 0014-4800

IS - 1

ER -