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Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer
  1. P Parrella1,
  2. P Mazzarelli2,*,
  3. E Signori2,5,
  4. G Perrone4,
  5. G F Marangi3,
  6. C Rabitti4,
  7. M Delfino6,
  8. M Prencipe1,
  9. A P Gallo1,
  10. M Rinaldi5,
  11. G Fabbrocini6,
  12. S Delfino3,
  13. P Persichetti3,
  14. V M Fazio1,2
  1. 1Oncology Research Laboratory, IRCCS Hospital “Casa Sollievo della Sofferenza”, San Giovanni Rotondo (FG), Italy
  2. 2CIR, Section for Molecular Medicine and Biotechnology, Campus Bio-Medico University, Rome, Italy
  3. 3Division of Plastic and Reconstructive Surgery, Campus Bio-Medico University, Rome, Italy
  4. 4Laboratory of Hystopathology, Campus Bio-Medico University, Rome, Italy
  5. 5CNR INMM, Laboratory of Gene Medicine, Area of Rome “Tar Vergata”, Rome, Italy
  6. 6Department of Dermatology, University Federico II, Naples, Italy
  1. Correspondence to:
    V M Fazio
    CIR, Section for Molecular Medicine and Biotechnology, Università Campus Bio-Medico, Via E Longoni 83, 00155 Rome, Italy; Fazio{at}unicampus.it

Abstract

Background: Experimental data suggest that exposure to ultraviolet radiation may indirectly induce DNA double-strand breaks.

Aim: To investigate the contribution of the non-homologous end-joining repair pathway in basal and squamous cell carcinomas.

Methods: Levels of Ku70 and Ku80 proteins were determined by immunohistochemical analysis and Ku70–Ku80 heterodimer-binding activity by electrophoretic mobility shift assay. Matched pathological normal margins and skin from healthy people were used as controls.

Results: A significant increase in Ku70 and Ku80 protein levels was found for both tumour types as compared with normal skin (p<0.001). Squamous cell carcinoma showed increased immunostaining as compared with basal cell tumours (p<0.02). A direct correlation was found between Ku70 and Ku80 protein levels and expression of the proliferation markers Ki-67/MIB-1 (p<0.02 and p<0.002, respectively) in basal cell carcinoma. DNA binding activity was increased in basal cell carcinoma samples as compared with matched skin histopathologically negative for cancer (p<0.006). In squamous cell carcinomas, however, the difference was significant only with normal skin (p<0.02) and not with matched pathologically normal margins.

Conclusions: Overall, an up regulation of the Ku70 and Ku80 protein levels seems to correlate only with tumour proliferation rate. As non-homologous end joining is an error-prone mechanism, its up regulation may ultimately increase genomic instability, contributing to tumour progression.

  • BCC, basal cell carcinoma
  • DSB, double-strand break
  • EMSA, electrophoretic mobility shift assay
  • IHC, immunohistochemical
  • NHEJ, non-homologous end joining
  • NMSC, non-melanoma skin cancer
  • SCC, squamous cell carcinoma
  • TBS, TRIS-buffered saline

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Footnotes

  • * Present affiliation: University of Rome “Tor Vergata”, Rome, Italy.

  • Published Online First 23 February 2006

  • Competing interests: None declared.

  • P Parrella and P Mazzarelli contributed equally to this work.

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