Insulin-like growth factor I receptor is expressed at normal levels in Nijmegen breakage syndrome cells.
Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder sharing a pleiotropic phenotype with ataxia-telangiectasia (A-T), including increased radiosensitivity and cancer disposition. Insulin-like growth factor I receptor (IGF-IR) expression is reportedly decreased in A-T cells, which is thought to contribute to its increased radiosensitivity. In this study, we investigated whether the same mechanism underlies the radiosensitivity of NBS cells. GM7166VA7 cells lacking NBS1 protein displayed a phenotype of increased radiosensitivity, while the introduction of NBS1 cDNA conferred radioresistance comparable to normal cells. IGF-IR expression levels were essentially the same among normal, NBS, and NBS1-complemented NBS cells. There was no significant difference between NBS and NBS1-complemented cells in activation of major downstream pathways of IGF-IR upon IGF-I stimulation, including phosphatidylinositol-3(') kinase (PI3-K) and mitogen-activated protein kinase (MAPK). Collectively, IGF-IR-related events are unlikely to be disrupted in NBS cells, and therefore, defects in IGF-IR signaling do not explain the increased radiosensitivity of NBS cells.
Watanabe
Hiroshi
H
Oral and Maxillofacial Radiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, Japan.
Yu
Dong
D
Sasaki
Takehito
T
Shibuya
Hitoshi
H
Hosoi
Yoshio
Y
Asada
Minoru
M
Komatsu
Kenshi
K
Miura
Masahiko
M
D002461:Cell Line, Transformed; D019457:Chromosome Breakage; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020935:MAP Kinase Signaling System; D011485:Protein Binding; D011836:Radiation Tolerance / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction; D013577:Syndrome
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1