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Contrasting DNA damage checkpoint responses in epithelium of the human seminal vesicle and prostate
Author(s) -
Jäämaa Sari,
Sankila Anna,
Rantanen Ville,
Peltonen Karita,
Järvinen Päivi M.,
af Hällström Taija M.,
Ruutu Mirja,
Taari Kimmo,
Andersson Leif C.,
Laiho Marikki
Publication year - 2011
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21509
Subject(s) - seminal vesicle , prostate , prostate cancer , epithelium , biology , dna damage , microbiology and biotechnology , cell cycle checkpoint , cancer research , cell cycle , cell , cancer , dna , genetics
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. DISCUSSION 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. Prostate 72:1060–1070, 2012. © 2011 Wiley Periodicals, Inc.