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Titolo:
Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies
Autore:
Pucci, S; Mazzarelli, P; Rabitti, C; Giai, M; Gallucci, M; Flammia, G; Alcini, A; Altomare, V; Fazio, VM;
Indirizzi:
CNR, Inst Expt Med, I-00133 Rome, Italy CNR Rome Italy I-00133CNR, Inst Expt Med, I-00133 Rome, Italy Lab Mol Med & Biotechnol, I-00155 Rome, Italy Lab Mol Med & Biotechnol Rome Italy I-00155 technol, I-00155 Rome, Italy Lab Histopathol, I-00155 Rome, Italy Lab Histopathol Rome Italy I-00155Lab Histopathol, I-00155 Rome, Italy Dept Urol, I-00155 Rome, Italy Dept Urol Rome Italy I-00155Dept Urol, I-00155 Rome, Italy Dept Gen Surg, I-00155 Rome, Italy Dept Gen Surg Rome Italy I-00155Dept Gen Surg, I-00155 Rome, Italy IRCCS H Casa Sollievo Sofferenza, Lab Mol Pathol, I-71013 San Giovanni Rotondo, FG, Italy IRCCS H Casa Sollievo Sofferenza San Giovanni Rotondo FG Italy I-71013 ly
Titolo Testata:
ONCOGENE
fascicolo: 6, volume: 20, anno: 2001,
pagine: 739 - 747
SICI:
0950-9232(20010208)20:6<739:TSMOKD>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; KU-PROTEIN; V(D)J RECOMBINATION; PROGNOSTIC MARKERS; CELL-SURFACE; ANTIGEN-KU; CANCER; AUTOANTIGEN; REPAIR;
Keywords:
Ku70/80 heterodimer; DNA repair; DNA double-strand breaks; DNA-PK; human tumors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Fazio, VM CNR, Inst Expt Med, Via Fosso Cavaliere 100, I-00133 Rome, ItalyCNR Via Fosso Cavaliere 100 Rome Italy I-00133 0133 Rome, Italy
Citazione:
S. Pucci et al., "Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies", ONCOGENE, 20(6), 2001, pp. 739-747

Abstract

The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein kinase (DNA-PK) and its DNA-binding activity mediates DNA double-strand breaks repair. Although Ku80 was recently proposed as a caretaker gene involved in the control of genome integrity, no data are available on Ku70/80DNA-binding activity in human tumors. Heterodimer DNA-binding activity andprotein expression were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder primary tumors and three metastatic nodes from breast cancers. Corresponding normal tissues of the same patients were used as controls. Ten out of 15 tumors showed nuclear Ku-binding activity 3-10 times higher than in the normal tissues, irrespective of bladder or breast origin. Conversely, in 5/15 primary tumors and in all the metastatic nodes analysed, nuclear Ku-activity was 1.5-4.5-fold lower than in the corresponding normal tissues. Cytoplasmic heterodimer activity significantly differed between tumor and normal tissues, displaying a 2-10-fold increase in neoplastic tissues. Three different patterns combining both Ku expression and activity with tumor characteristics were identified. In low aggressive breast tumors p70/p80 proteins were expressed in tumor but not in normal tissues. The heterodimer binding-activity matched the protein levels. In non-invasivebladder carcinomas no significant differences in protein expression between tumor and the corresponding normal tissues were found, however heterodimer binding-activity was increased in tumor samples. In breast and bladder tumors, at the advanced stage and in node metastases, the binding activity was strongly reduced in tumor biopsies, however no differences mere demonstrated between normal and tumor protein levels, Our results suggest a different modulation of Ku70/80 DNA-binding activity in human neoplastic tissues, possibly related to tumor progression. Findings provide further data on tissue-specific protein expression and post-translational regulation of heterodimer activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 18:14:57