Signal transduction pathway to low-dose radiation-induced apoptosis in peripheral PNET cells.
We investigated the signal transduction pathway to low-dose radiation-induced apoptosis in vitro in the human peripheral primitive neuroectodermal tumor (pPNET) cell line with wild-type p53 established in our laboratory. Apoptosis was induced by 2Gy irradiation in an almost p53-dependent manner in this model except for a deficiency of the cleavage of caspase-9. It was detected 3 hours after irradiation by fragmentation assay. The expressions of p53, p21WAF-1 and Bax increased, in contrast to the gradually decreasing expression of Bcl-2, as observed by immunoblotting. Following this, cleavages of caspase-3 and PARP reached peak levels. There were no detectable increases in ERK expression and caspase-9 cleavage. In respect of the probability of other pathways to apoptosis, this cell line will provide a useful model both for investigating low-dose radiation-induced signal transduction pathway and for analyzing the biological characteristics of pPNET.
Imai
Reiko
R
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8111, Japan.
Akimoto
Tetsuo
T
Maebayashi
Katsuya
K
Ishikawa
Hitoshi
H
Sakurai
Hideyuki
H
Saitoh
Jun-Ichi
J
Hasegawa
Masatoshi
M
Mitsuhashi
Norio
N
Nakano
Takashi
T
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018242:Neuroectodermal Tumors, Primitive / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D009918:Orbital Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D010766:Phosphorylation / Q000528:radiation effects; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D061945:Caspase Inhibitors; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases