TY - JOUR
T1 - Maintenance of genomic integrity after DNA double strand breaks in the human prostate and seminal vesicle epithelium
T2 - The best and the worst
AU - Jäämaa, Sari
AU - Laiho, Marikki
N1 - Funding Information:
Leif C. Andersson is acknowledged for providing the tissue material in Figures 1 and 2 . SJ has received financial support from Finnish Cultural Foundation, Ida Montin Foundation, K. Albin Foundation and Maud Kuistila Foundation, and ML from Academy of Finland, Patrick C. Walsh Prostate Cancer Foundation and Prostate Cancer SPORE (5P50CA58236), which are gratefully acknowledged.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - Androgen signaling
KW - Cancer
KW - Cell cycle checkpoint
KW - DNA damage
KW - DNA double strand break
KW - Repair
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U2 - 10.1016/j.molonc.2012.06.001
DO - 10.1016/j.molonc.2012.06.001
M3 - Review article
C2 - 22762987
AN - SCOPUS:84866013135
SN - 1574-7891
VL - 6
SP - 473
EP - 483
JO - Molecular oncology
JF - Molecular oncology
IS - 5
ER -