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.
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark.
authors.forename: Ann-Katrine
authors.initials: AK
authors.lastname: Jakobsen
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark.
authors.forename: Kristina Lystlund
authors.initials: KL
authors.lastname: Lauridsen
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark.
authors.forename: Evelyn Benuja
authors.initials: EB
authors.lastname: Samuel
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark.
authors.forename: Joanna
authors.initials: J
authors.lastname: Proszek
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Denmark; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Denmark.
authors.forename: Birgitta Ruth
authors.initials: BR
authors.lastname: Knudsen
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark; Department of Clinical Pathology, Vejle Hospital, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hager
authors.affiliation: Department of Pathology, Aarhus University Hospital, Denmark. Electronic address: magnstou@rm.dk.
authors.forename: Magnus
authors.initials: M
authors.lastname: Stougaard
mesh_terms: D015374:Biosensing Techniques; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D004249:DNA Damage; D004261:DNA Replication; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006801:Humans; D036103:Nanotechnology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D010727:Phosphoric Diester Hydrolases; C498508:TDP1 protein, human; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human
keywords: Biosensor; Cryosection; Lung cancer; Topoisomerase I; Tyrosyl-DNA phosphodiesterase 1