- Tytuł:
- Relationships between EGFR-initiated signalling, DNA double-strand break rejoining and survival in X-irradiated human glioma M059 cells
- Autorzy:
-
Grądzka, I.
Buraczewska, I.
Szumiel, I. - Powiązania:
- https://bibliotekanauki.pl/articles/146764.pdf
- Data publikacji:
- 2008
- Wydawca:
- Instytut Chemii i Techniki Jądrowej
- Tematy:
-
human glioma M059 K and J cells
DNA-dependent protein kinase (DNA-PK)
radiosensitivity
DNA double-strand break (DSB) rejoining
epidermal-growth-factor-receptor (EGFR)
signalling inhibitors: tyrphostin - Opis:
- The aim of this study was to investigate the effect of signalling inhibition on survival and double-strand break (DSB) rejoining in cells differing in sensitivity to inhibitors, X-rays and bleomycin. Human glioma M059 cells, K (relatively radioresistant) and J (radiosensitive, defective in DSB rejoining for lack of DNA-dependent protein kinase catalytic subunit, DNA-PKcs) were pretreated with signalling inhibitors: tyrphostin AG 1478, specific for epidermalgrowth- factor-receptor (EGFR) kinase or PD 98059, specific for kinase MEK 1/2 (mitogen-activated, extracellular signal-activated kinases 1 and 2). Subsequently, the cells were X-irradiated or treated with bleomycin. Cell survival was determined by clonogenicity test. DSB rejoining was monitored with the use of pulsed-field gel electrophoresis (PFGE). We found that in X-irradiated M059 K cells EGFR kinase activity was necessary for efficient DSB rejoining and the kinase inhibitor, tyrphostin AG 1478, acted as radiosensitizer in the dose range that reduced cell survival to 0.7-0.8. Inhibition of EGFR kinase, however, did not decrease survival or affect DSB rejoining in DNA-PKcs-deficient M059 J cells. These results indicated that the decrease in cell survival was due to a disturbed DSB rejoining by the DNA-PK dependent system. In contrast, inhibition of MEK 1/2 kinase on EGFR downstream signalling pathway by PD 98059 did not affect DSB rejoining in either cell line and exerted a radioprotective effect.
- Źródło:
-
Nukleonika; 2008, 53, 2; 37-44
0029-5922
1508-5791 - Pojawia się w:
- Nukleonika
- Dostawca treści:
- Biblioteka Nauki
Artykuł