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  • Original Paper
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Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies

Oncogene volume 20, pages 739–747 (2001)Cite this article

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 Ku70/80 DNA-binding activity in human tumors. Heterodimer DNA-binding activity and protein 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-invasive bladder 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 were 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.

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Acknowledgements

This work was partly supported by grant IRCCS/RC/1999 from the Italian Ministry of Health.

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Authors and Affiliations

  1. Institute of Experimental Medicine, CNR, Rome, 00133, Italy

    S Pucci, P Mazzarelli & V M Fazio

  2. Laboratory for Molecular Medicine and Biotechnology, Campus Bio Medico University, Rome, 00155, Italy

    P Mazzarelli & V M Fazio

  3. Laboratory of Histopathology, Campus Bio Medico University, Rome, 00155, Italy

    C Rabitti

  4. Department of Obstetrics and Gynecology, Mauriziano H. ‘Umberto I’, 10100 (TO), Italy

    M Giai

  5. Department of Urology, Campus Bio Medico University, Rome, Italy, 00155

    M Gallucci, G Flammia & A Alcini

  6. Department of General Surgery, Campus Bio Medico University, Rome, 00155

    V Altomare

  7. Laboratory for Molecular Pathology, IRCCS H. ‘Casa Sollievo Sofferenza’, San Giovanni Rotondo, 71013 (FG), Italy

    V M Fazio

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  1. S Pucci
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Pucci, S., Mazzarelli, P., Rabitti, C. et al. Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies. Oncogene 20, 739–747 (2001). https://doi.org/10.1038/sj.onc.1204148

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