Radiosensitization by overexpression of the nonphosphorylation form of IkappaB-alpha in human glioma cells.
To assess the role of NF-kappaB in cellular radiosensitivity, we constructed mutated IkappaB expression plasmids for SY-IkappaB (with mutations at residues of 32, 36 and 42) expression in human malignant glioma cells (radiosensitive MO54 and radioresistant T98 cells), giving respective cell types referred to as MO54-SY4 and T98-SY14. Both of the clones expressing SY-IkappaB became radiosensitive, compared with the parental MO54 and T98 cells. A treatment with herbimycin A or genistein did not change the radiosensitivity of cells expressing SY-IkappaB, but made both the MO54 and T98 parental cells more sensitive to ionizing radiation. A treatment with TNF-alpha induced DNA fragmentation and apoptosis in cells expressing SY-IkappaB, but not in MO54 and T98 cells. The survival after X-ray exposure of the parental MO54 cells was slightly increased by a TNF-alpha treatment, but that of the parental T98 cells did not change. The change in sensitivity to ultra-violet (UV) radiation and adriamycin in MO54-SY4 cells was very similar to that for X-ray sensitivity, but no change was observed in T98-SY14 cells. Significant sublethal damage repair was observed in T98 cells, whereas MO54 cells showed little repair activity. The expression of p53 was enhanced in the parental MO54 cells, while the p53 levels in the MO54-SY4, and in the parent and clonal T98 cells, did not change. Our data suggest that the serine and tyrosine phosphorylation of IkappaB-alpha may play a role in determining the radiosensitivity of malignant glioma cells.
Honda
Naoko
N
Department Radiation Genetics, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-Ku, Kyoto 606-8501, Japan.
Yagi
Kasumi
K
Ding
Gui-Rong
GR
Miyakoshi
Junji
J
D005910:Glioma / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D011838:Radiation-Sensitizing Agents / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D011838:Radiation-Sensitizing Agents; D000072000:NF-KappaB Inhibitor alpha