Digestive Diseases and Sciences

, Volume 58, Issue 9, pp 2615–2622

Colonic 15-PGDH Levels Are Stable Across Distance and Time and Are Not Perturbed by Aspirin Intervention

  • Stephen P. Fink
  • Dong-Hoon Yang
  • Jill S. Barnholtz-Sloan
  • Yeon-Mi Ryu
  • Debra Mikkola
  • John D. Potter
  • Johanna W. Lampe
  • Sanford D. Markowitz
  • Seung-Jae Myung
Original Article

DOI: 10.1007/s10620-013-2670-5

Cite this article as:
Fink, S.P., Yang, DH., Barnholtz-Sloan, J.S. et al. Dig Dis Sci (2013) 58: 2615. doi:10.1007/s10620-013-2670-5

Abstract

Background and Aims

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.

Keywords

Colon cancer 15-PGDH NSAIDs Biomarker 

Abbreviations

15-PGDH

15-Hydroxyprostaglandin dehydrogenase

COX-1

Cyclooxygenase-1

COX-2

Cyclooxygenase-2

TGFBR2

TGF-beta type II receptor

Supplementary material

10620_2013_2670_MOESM1_ESM.eps (2 mb)
Supplementary material 1 (EPS 2091 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Stephen P. Fink
    • 1
    • 2
  • Dong-Hoon Yang
    • 3
  • Jill S. Barnholtz-Sloan
    • 2
  • Yeon-Mi Ryu
    • 3
  • Debra Mikkola
    • 1
    • 2
  • John D. Potter
    • 4
    • 5
  • Johanna W. Lampe
    • 4
  • Sanford D. Markowitz
    • 1
    • 2
  • Seung-Jae Myung
    • 3
  1. 1.Department of MedicineCase Western Reserve University and Case Medical CenterClevelandUSA
  2. 2.Case Comprehensive Cancer CenterCase Western Reserve University and Case Medical CenterClevelandUSA
  3. 3.Division of Gastroenterology, Asan Digestive Disease Research Institute, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  4. 4.Fred Hutchinson Cancer Research CenterSeattleUSA
  5. 5.Centre for Public Health Research, Massey UniversityWellingtonNew Zealand

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