title: Colonic 15-PGDH levels are stable across distance and time and are not perturbed by aspirin intervention.
abstract: OBJECTIVE
  15-Hydroxprostaglandin dehydrogenase (15-PGDH) mediates a colon neoplasia suppressor pathway, acting through metabolic antagonism of cyclooxygenase-mediated colon carcinogenesis. To determine whether the colon tumor prevention activity of 15-PGDH acts as a constant or variable effect among individuals, we determined whether 15-PGDH levels remain stable over subsite and time in the human colon, determined the extent of differences in 15-PGDH levels between different individuals, and determined whether 15-PGDH modulation mediates any part of the anti-colon tumor effect of aspirin.
  
  
  METHODS
  Using real-time PCR, we measured 15-PGDH mRNA to determine the correlation of 15-PGDH level in replicate colon biopsies, in biopsies from throughout the length of the colon, in repeat biopsies taken 4 months apart, and in paired biopsies of individuals taken before and after aspirin treatment, and by Western-blot for 15-PGDH protein in mice.
  
  
  RESULTS
  Colonic 15-PGDH levels varied 4.4-fold across the human population. Within individuals, 15-PGDH levels proved highly reproducible (r=0.81 in duplicate biopsies) and stable along the length of the colon, with average 15-PGDH levels deviating by only 17% from rectum to cecum. An individual's 15-PGDH levels are also highly stable over time, with a median coefficient of variation over a 4-month interval of only 12%. Last, colonic 15-PGDH levels proved resistant to alteration by aspirin, with only a 10% difference in 15-PGDH levels measured before and after aspirin treatment.
  
  
  CONCLUSIONS
  15-PGDH levels vary across the population in a stable and reproducible manner, and are resistant to alteration by aspirin. 15-PGDH represents an independent target for modulation by candidate colon tumor chemopreventive agents.
authors.affiliation: Department of Medicine, Case Western Reserve University and Case Medical Center, 10900 Euclid Ave., Wolstein Research Building, Rm 3-128, Cleveland, OH 44106-7285, USA. stephen.fink@case.edu
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Fink
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Yang
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.forename: Yeon-Mi
authors.initials: YM
authors.lastname: Ryu
authors.forename: Debra
authors.initials: D
authors.lastname: Mikkola
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Johanna W
authors.initials: JW
authors.lastname: Lampe
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Myung
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use*; D018890:Chemoprevention; D003106:Colon / Q000187:drug effects / Q000201:enzymology*; D003110:Colonic Neoplasms / Q000517:prevention & control*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012007:Rectum / Q000201:enzymology
chemical_list: D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D001241:Aspirin