TY - JOUR
T1 - Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma
AU - Stronati, Laura
AU - Gensabella, Giuseppe
AU - Lamberti, Claudia
AU - Barattini, Paola
AU - Frasca, Daniela
AU - Tanzarella, Caterina
AU - Giacobini, Stefano
AU - Toscano, Maria Gabriella
AU - Santacroce, Criselda
AU - Danesi, Donatella Tirindelli
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2001/11/1
Y1 - 2001/11/1
N2 - BACKGROUND. The Ku protein is a tightly associated heterodimer, comprised of 70-kilodalton (kD) and 86-kD subunits, that forms the DNA-dependent protein kinase (DNA-PK) complex together with the 470-kD DNA-PKcs catalytic subunit, and is involved mainly in DNA double-strand breaks (DSBs) repair. The objective of the current study was to investigate the expression and DNA-binding activity of the Ku protein in fresh tissues from patients with bladder carcinoma and to compare it with that in nontumor tissues obtained from the same organ. Moreover, the DNA-binding activity of Ku was assessed after exposure of the tumor cells to 1 or 2 grays (Gy) of X-rays. Furthermore, the level of phosphorylated Ku was analyzed in both the nuclear and cytoplasmic compartment of normal tissue after exposure to 2 Gy of X-rays. METHODS. The expression and DNA-binding activity of Ku protein were assessed in tumor samples from patients who all were diagnosed with transitional cell carcinoma (TCC) of the bladder using Western blot analysis and the electrophoretic mobility shift assay, respectively. RESULTS. Enhanced Ku activity and expression were found in tumor tissue compared with normal tissue for each patient. Moreover, variations in Ku activity were found in a dose-dependent manner after the tumor cells were exposed to 1 or 2 Gy of X-rays. A decrease in phosphorylated Ku in the cytoplasm and a parallel increase in the nucleus of normal tissue cells were observed after exposure to X-rays. CONCLUSIONS. The results of the current study suggest a possible role of Ku in regulating the DNA-PK activity of DSBs repair in bladder tumors.
AB - BACKGROUND. The Ku protein is a tightly associated heterodimer, comprised of 70-kilodalton (kD) and 86-kD subunits, that forms the DNA-dependent protein kinase (DNA-PK) complex together with the 470-kD DNA-PKcs catalytic subunit, and is involved mainly in DNA double-strand breaks (DSBs) repair. The objective of the current study was to investigate the expression and DNA-binding activity of the Ku protein in fresh tissues from patients with bladder carcinoma and to compare it with that in nontumor tissues obtained from the same organ. Moreover, the DNA-binding activity of Ku was assessed after exposure of the tumor cells to 1 or 2 grays (Gy) of X-rays. Furthermore, the level of phosphorylated Ku was analyzed in both the nuclear and cytoplasmic compartment of normal tissue after exposure to 2 Gy of X-rays. METHODS. The expression and DNA-binding activity of Ku protein were assessed in tumor samples from patients who all were diagnosed with transitional cell carcinoma (TCC) of the bladder using Western blot analysis and the electrophoretic mobility shift assay, respectively. RESULTS. Enhanced Ku activity and expression were found in tumor tissue compared with normal tissue for each patient. Moreover, variations in Ku activity were found in a dose-dependent manner after the tumor cells were exposed to 1 or 2 Gy of X-rays. A decrease in phosphorylated Ku in the cytoplasm and a parallel increase in the nucleus of normal tissue cells were observed after exposure to X-rays. CONCLUSIONS. The results of the current study suggest a possible role of Ku in regulating the DNA-PK activity of DSBs repair in bladder tumors.
KW - Bladder carcinoma
KW - DNA binding activity
KW - DNA double-strand breaks (DSBs) repair
KW - DNA-dependent protein kinase (DNA-PK)
KW - Ionizing radiation
KW - Ku 70/80
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U2 - 10.1002/1097-0142(20011101)92:9<2484::AID-CNCR1598>3.0.CO;2-7
DO - 10.1002/1097-0142(20011101)92:9<2484::AID-CNCR1598>3.0.CO;2-7
M3 - Article
C2 - 11745306
AN - SCOPUS:0035498628
VL - 92
SP - 2484
EP - 2492
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 9
ER -