Maintenance of genomic integrity after DNA double strand breaks in the human prostate and seminal vesicle epithelium: The best and the worst

Sari Jäämaa, Marikki Laiho

Research output: Contribution to journalReview article

Abstract

Prostate cancer is one of the most frequent cancer types in men, and its incidence is steadily increasing. On the other hand, primary seminal vesicle carcinomas are extremely rare with less than 60 cases reported worldwide. Therefore the difference in cancer incidence has been estimated to be more than a 100,000-fold. This is astonishing, as both tissues share similar epithelial structure and hormonal cues. Clearly, the two epithelia differ substantially in the maintenance of genomic integrity, possibly due to inherent differences in their DNA damage burden and DNA damage signaling. The DNA damage response evoked by DNA double strand breaks may be relevant, as their faulty repair has been implicated in the formation of common genomic rearrangements such as TMPRSS2-ERG fusions during prostate carcinogenesis. Here, we review DNA damaging processes of both tissues with an emphasis on inflammation and androgen signaling. We discuss how benign prostate and seminal vesicle epithelia respond to acute DNA damage, focusing on the canonical DNA double strand break-induced ATM-pathway, p53 and DNA damage induced checkpoints. We propose that the prostate might be more prone to the accumulation of genetic aberrations during epithelial regeneration than seminal vesicles due to a weaker ability to enforce DNA damage checkpoints.

Original languageEnglish (US)
Pages (from-to)473-483
Number of pages11
JournalMolecular oncology
Volume6
Issue number5
DOIs
StatePublished - Oct 2012

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Keywords

  • Androgen signaling
  • Cancer
  • Cell cycle checkpoint
  • DNA damage
  • DNA double strand break
  • Repair

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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