CC BY-NC-ND 4.0 · Laryngorhinootologie 2021; 100(S 02): S126
DOI: 10.1055/s-0041-1727974
Abstracts
Head-Neck-Oncology: HPV / Tumor Marker

A lack of effectiveness in the ATM-orchestrated DNA damage response contributes to the enhanced radiation sensitivity of HPV-positive HNSCC cell lines

T Rieckmann
1   Universitätsklinikum Hamburg-Eppendorf, Klinik für Hals-, Nasen- und Ohrenheilkunde, Hamburg
,
H Zech
1   Universitätsklinikum Hamburg-Eppendorf, Klinik für Hals-, Nasen- und Ohrenheilkunde, Hamburg
,
S Köcher
2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie, Hamburg
,
C Betz
1   Universitätsklinikum Hamburg-Eppendorf, Klinik für Hals-, Nasen- und Ohrenheilkunde, Hamburg
,
L Krug
2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie, Hamburg
,
F Meyer
2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie, Hamburg
,
M Kriegs
2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie, Hamburg
,
K Rothkamm
2   Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie, Hamburg
› Author Affiliations
› Further Information
Also available at
 
 

    Background Patients with HPV-positive (HPV+) HNSCC show a favorable prognosis. We had previously shown, that HPV+ HNSCC cell lines are characterized by an enhanced radiation sensitivity and decreased DNA double-strand break (DSB) repair capacity. Various publications have suggested the dysregulated, mostly decreased expression of a number of DNA repair factors as the underlying cause but the evidence was mostly based on a very low number of cell lines. Methods Comparison of protein expression and assessment of ATM-dependent phosphorylation through Western blot. Analysis of DNA repair through immunofluorescence microscopy of DSB repair foci. Analysis of radiosensitivity through colony formation assays and of radiation induced DNA endresection through flow cytometry. ResultsComparing the expression levels of repair factors, whose dysregulation was reported to cause the radiosensitivity of HPV+ HNSCC, we could not substantiate most published findings. Our screen revealed minimal expression of the central DNA damage response kinase, ATM, in the most radiosensitive HPV+ strains. Sensitive HPV+ cells ahowed DNA DSB repair kinetics similar to ATM-deficient cells. ATM inhibition was far less effective in HPV+ cells with regard to DSB repair and cell survival after radiation. Unexpectedly, we did not find a defect in the phosphorylation of ATM targets and ATM-dependent DNA endresection, a critical step of homologous recombination, was similarly inhibited in both cell types upon ATM-inhibition.

    ConclusionThe reduced effectiveness of ATM-inhibition points towards an impairment in the ATM-orchestrated DNA damage response but direct endpoints suggest ATM is generally functional in HPV+ cells. Therefore, the exact molecular mechanisms need to be further explored.

    Poster-PDF A-1738.pdf

    Erich und Gertrud Roggenbuck-Stiftung sowie Brigitte und Dr. Konstanze Wegener-Stiftung


    #

    Conflict of interest

    Der Erstautor gibt keinen Interessenskonflikt an.

    Address for correspondence

    Dr. phil.nat. Rieckmann Thorsten
    Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie
    Hamburg

    Publication History

    Article published online:
    13 May 2021

    © 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

    Georg Thieme Verlag KG
    Rüdigerstraße 14, 70469 Stuttgart, Germany