title: Contrasting DNA damage checkpoint responses in epithelium of the human seminal vesicle and prostate.
abstract: BACKGROUND
  Prostate and seminal vesicle are two similar hormone responsive human organs that differ dramatically in their cancer incidence. DNA damage response (DDR) is required for maintenance of genomic integrity.
  
  
  METHODS
  In this study we investigated the DDR and cell cycle checkpoint activation of these organs using orthotopic cultures of human surgery-derived tissues and primary cultures of isolated prostate and seminal vesicle cells.
  
  
  RESULTS
  We find that the activation of ATM signaling pathway by ionizing radiation (IR) was comparable in both tissues. Previously, we have shown that the prostate secretory cells express low levels of histone variant H2AX and phosphorylated H2AX (γH2AX) after IR. Here we demonstrate that H2AX levels are low also in the secretory seminal vesicle cells suggesting that this is a common phenotype of postmitotic cells. We consequently established primary epithelial cell cultures from both organs to compare their DDR. Interestingly, contrary to human prostate epithelial cells (HPEC), primary seminal vesicle epithelial cells (HSVEC) displayed effective cell cycle checkpoints after IR and expressed higher levels of Wee1A checkpoint kinase. Furthermore, HSVEC but not HPEC cells were able to activate p53 and to induce p21 cell cycle inhibitor.
  
  
  CONCLUSIONS
  Our results show that during replication, the checkpoint enforcement is more proficient in the seminal vesicle than in the prostate epithelium cells. This indicates a more stringent enforcement of DDR in replicating seminal vesicle epithelial cells, and suggests that epithelial regeneration combined with sub-optimal checkpoint responses may contribute to high frequency of genetic lesions in the prostate epithelium.
authors.affiliation: Molecular Cancer Biology Program and Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Sari
authors.initials: S
authors.lastname: Jäämaa
authors.forename: Anna
authors.initials: A
authors.lastname: Sankila
authors.forename: Ville
authors.initials: V
authors.lastname: Rantanen
authors.forename: Karita
authors.initials: K
authors.lastname: Peltonen
authors.forename: Päivi M
authors.initials: PM
authors.lastname: Järvinen
authors.forename: Taija M
authors.initials: TM
authors.lastname: Af Hällström
authors.forename: Mirja
authors.initials: M
authors.lastname: Ruutu
authors.forename: Kimmo
authors.initials: K
authors.lastname: Taari
authors.forename: Leif C
authors.initials: LC
authors.lastname: Andersson
authors.forename: Marikki
authors.initials: M
authors.lastname: Laiho
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002478:Cells, Cultured; D004249:DNA Damage / Q000235:genetics*; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology*; D004848:Epithelium / Q000473:pathology / Q000502:physiology; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology / Q000502:physiology*; D012669:Seminal Vesicles / Q000473:pathology / Q000502:physiology*