The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis
Open accessAbstract
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is a prostaglandin-degrading enzyme that is highly expressed in normal colon mucosa but is ubiquitously lost in human colon cancers. Herein, we demonstrate that 15-PGDH is active in vivo as a highly potent suppressor of colon neoplasia development and acts in the colon as a required physiologic antagonist of the prostaglandin-synthesizing activity of the cyclooxygenase 2 (COX-2) oncogene. We first show that 15-PGDH gene knockout induces a marked 7.6-fold increase in colon tumors arising in the Min (multiple intestinal neoplasia) mouse model. Furthermore, 15-PGDH gene knockout abrogates the normal resistance of C57BL/6J mice to colon tumor induction by the carcinogen azoxymethane (AOM), conferring susceptibility to AOM-induced adenomas and carcinomas in situ . Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E 2 in 15-PGDH null colonic mucosa. A parallel role for 15-PGDH loss in promoting the earliest steps of colon neoplasia in humans is supported by our finding of a universal loss of 15-PGDH expression in microscopic colon adenomas recovered from patients with familial adenomatous polyposis, including adenomas as small as a single crypt. These models thus delineate the in vivo significance of 15-PGDH-mediated negative regulation of the COX-2 pathway and moreover reveal the particular importance of 15-PGDH in opposing the neoplastic progression of colonic aberrant crypt foci.
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Cites
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Treatment of Colonic and Rectal Adenomas with Sulindac in Familial Adenomatous Polyposis
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Multiple Intestinal Neoplasia Caused by a Mutation in the Murine Homolog of the APC Gene
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Acceleration of intestinal polyposis through prostaglandin receptor EP2 in ApcΔ716 knockout mice
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Cited by
Molecular Basis of Colorectal Cancer
Markowitz, S. D., & Bertagnolli, M. M. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804588 · Cited by 2,052
Self-citationGreenhough, A., Smartt, H. J. M., Moore, A. E., Roberts, H. R., Williams, A. C., Paraskeva, C., & Kaidi, A. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp014 · Cited by 1,220
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The role of COX‐2 in intestinal inflammation and colorectal cancer
Wang, D., & DuBois, R. N. (2010) · Oncogene · doi:10.1038/onc.2009.421 · Cited by 805
Multifaceted roles of PGE2 in inflammation and cancer
Nakanishi, M., & Rosenberg, D. W. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-012-0342-8 · Cited by 591
Metadata
- Authors
- Myung, S.-J., Rerko, R. M., Yan, M., Platzer, P., Guda, K., Dotson, A., Lawrence, E., Dannenberg, A. J., Lovgren, A. K., Luo, G., Pretlow, T. P., Newman, R. A., Willis, J., Dawson, D., & Markowitz, S. D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-08-08
- Volume
- 103
- Issue
- 32
- Pages
- 12098-12102
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2157341902
- Cited by
- 264
- References
- 24
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Open access
- green
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- Myung, S.-J., Rerko, R. M., Yan, M., Platzer, P., Guda, K., Dotson, A., Lawrence, E., Dannenberg, A. J., Lovgren, A. K., Luo, G., Pretlow, T. P., Newman, R. A., Willis, J., Dawson, D., & Markowitz, S. D. (2006). 15-Hydroxyprostaglandin dehydrogenase is an in vivo suppressor of colon tumorigenesis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0603235103
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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