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

Autor: Fink, Stephen, Yang, Dong-Hoon, Barnholtz-Sloan, Jill, Ryu, Yeon-Mi, Mikkola, Debra, Potter, John, Lampe, Johanna, Markowitz, Sanford, Myung, Seung-Jae
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Zdroj: Digestive Diseases & Sciences; Sep2013, Vol. 58 Issue 9, p2615-2622, 8p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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