Non-muscle invasive bladder cancer tissues have increased base excision repair capacity


Somuncu B., Keskin M. S. , Antmen F. M. , Sağlıcan Y. , Ekmekçioğlu A., Ertüzün T., ...More

Scientific Reports, vol.10, no.1, pp.16371-16387, 2020 (Journal Indexed in SCI)

  • Publication Type: Article / Article
  • Volume: 10 Issue: 1
  • Publication Date: 2020
  • Title of Journal : Scientific Reports
  • Page Numbers: pp.16371-16387

Abstract

The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence cancer susceptibility, recurrence, and progression, as well as responses to chemotherapy and radiotherapy. We report herein that non-muscle invasive BC (NMIBC) tissues exhibit increased uracil incision, abasic endonuclease and gap-filling activities, as well as total BER capacity in comparison to normal bladder tissue from the same patient (p < 0.05). No significant difference was detected in 8-oxoG incision activity between cancer and normal tissues. NMIBC tissues have elevated protein levels of uracil DNA glycosylase, 8-oxoguanine DNA glycosylase, AP endonuclease 1 and DNA polymerase β protein. Moreover, the fold increase in total BER and the individual BER enzyme activities were greater in high-grade tissues than in low-grade NMIBC tissues. These findings suggest that enhanced BER activity may play a role in the etiology of NMIBC and that BER proteins could serve as biomarkers in disease prognosis, progression or response to genotoxic therapeutics, such as Bacillus Calmette-Guérin.