Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma

Laura Stronati, Giuseppe Gensabella, Claudia Lamberti, Paola Barattini, Daniela Frasca, Caterina Tanzarella, Stefano Giacobini, Maria Gabriella Toscano, Criselda Santacroce, Donatella Tirindelli Danesi

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2484-2492
Number of pages9
JournalCancer
Volume92
Issue number9
DOIs
StatePublished - Nov 1 2001
Externally publishedYes

Fingerprint

Urinary Bladder
Carcinoma
DNA
X-Rays
DNA-Activated Protein Kinase
Neoplasms
Double-Stranded DNA Breaks
Transitional Cell Carcinoma
Electrophoretic Mobility Shift Assay
Urinary Bladder Neoplasms
Ku Autoantigen
Catalytic Domain
Cytoplasm
Western Blotting

Keywords

  • Bladder carcinoma
  • DNA binding activity
  • DNA double-strand breaks (DSBs) repair
  • DNA-dependent protein kinase (DNA-PK)
  • Ionizing radiation
  • Ku 70/80

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Stronati, L., Gensabella, G., Lamberti, C., Barattini, P., Frasca, D., Tanzarella, C., ... Danesi, D. T. (2001). Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma. Cancer, 92(9), 2484-2492. https://doi.org/10.1002/1097-0142(20011101)92:9<2484::AID-CNCR1598>3.0.CO;2-7

Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma. / Stronati, Laura; Gensabella, Giuseppe; Lamberti, Claudia; Barattini, Paola; Frasca, Daniela; Tanzarella, Caterina; Giacobini, Stefano; Toscano, Maria Gabriella; Santacroce, Criselda; Danesi, Donatella Tirindelli.

In: Cancer, Vol. 92, No. 9, 01.11.2001, p. 2484-2492.

Research output: Contribution to journalArticle

Stronati, L, Gensabella, G, Lamberti, C, Barattini, P, Frasca, D, Tanzarella, C, Giacobini, S, Toscano, MG, Santacroce, C & Danesi, DT 2001, 'Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma', Cancer, vol. 92, no. 9, pp. 2484-2492. https://doi.org/10.1002/1097-0142(20011101)92:9<2484::AID-CNCR1598>3.0.CO;2-7
Stronati, Laura ; Gensabella, Giuseppe ; Lamberti, Claudia ; Barattini, Paola ; Frasca, Daniela ; Tanzarella, Caterina ; Giacobini, Stefano ; Toscano, Maria Gabriella ; Santacroce, Criselda ; Danesi, Donatella Tirindelli. / Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma. In: Cancer. 2001 ; Vol. 92, No. 9. pp. 2484-2492.
@article{7a85574f84104fe8bbf5aa1ad2f7313f,
title = "Expression and DNA binding activity of the Ku heterodimer in bladder carcinoma",
abstract = "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.",
keywords = "Bladder carcinoma, DNA binding activity, DNA double-strand breaks (DSBs) repair, DNA-dependent protein kinase (DNA-PK), Ionizing radiation, Ku 70/80",
author = "Laura Stronati and Giuseppe Gensabella and Claudia Lamberti and Paola Barattini and Daniela Frasca and Caterina Tanzarella and Stefano Giacobini and Toscano, {Maria Gabriella} and Criselda Santacroce and Danesi, {Donatella Tirindelli}",
year = "2001",
month = "11",
day = "1",
doi = "10.1002/1097-0142(20011101)92:9<2484::AID-CNCR1598>3.0.CO;2-7",
language = "English",
volume = "92",
pages = "2484--2492",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "9",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0035498628&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035498628&partnerID=8YFLogxK

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

VL - 92

SP - 2484

EP - 2492

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 9

ER -