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

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalExperimental and Molecular Pathology
Volume99
Issue number1
Pages (from-to)56-64
ISSN0014-4800
DOIs
Publication statusPublished - Aug 2015

Fingerprint

Type I DNA Topoisomerase
Tumors
Cells
Tissue
Neoplasms
Camptothecin
DNA
tyrosyl-DNA phosphodiesterase
Transcription
Catalysis
Assays
Repair
Topology
Cell Line

Keywords

  • Biosensor
  • Cryosection
  • Lung cancer
  • Topoisomerase I
  • Tyrosyl-DNA phosphodiesterase 1
  • Humans
  • DNA Replication
  • Phosphoric Diester Hydrolases/metabolism
  • Sensitivity and Specificity
  • Biosensing Techniques
  • DNA Topoisomerases, Type I/metabolism
  • Carcinoma, Non-Small-Cell Lung/enzymology
  • DNA Damage
  • Nanotechnology

Cite this

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. In: Experimental and Molecular Pathology. 2015 ; Vol. 99, No. 1. pp. 56-64.
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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.",
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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.

In: Experimental and Molecular Pathology, Vol. 99, No. 1, 08.2015, p. 56-64.

Research output: Contribution to journalJournal articleResearchpeer-review

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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 - 2015/8

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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.

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.

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KW - Cryosection

KW - Lung cancer

KW - Topoisomerase I

KW - Tyrosyl-DNA phosphodiesterase 1

KW - Humans

KW - DNA Replication

KW - Phosphoric Diester Hydrolases/metabolism

KW - Sensitivity and Specificity

KW - Biosensing Techniques

KW - DNA Topoisomerases, Type I/metabolism

KW - Carcinoma, Non-Small-Cell Lung/enzymology

KW - DNA Damage

KW - Nanotechnology

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DO - 10.1016/j.yexmp.2015.05.006

M3 - Journal article

C2 - 25987486

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SP - 56

EP - 64

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

SN - 0014-4800

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