15-hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer

Michael G. Backlund, Jason R. Mann, Vijaykumar R. Holla, F. Gregory Buchanan, Hsin Hsiung Tai, Erik S. Musiek, Ginger L. Milne, Sharada Katkuri, Raymond N. DuBois

    Research output: Contribution to journalArticlepeer-review

    229 Scopus citations

    Abstract

    Prostaglandin E2 (PGE2) can stimulate tumor progression by modulating several proneoplastic pathways, including proliferation, angiogenesis, cell migration, invasion, and apoptosis. Although steady-state tissue levels of PGE2 stem from relative rates of biosynthesis and breakdown, most reports examining PGE2 have focused solely on the cyclooxygenase-dependent formation of this bioactive lipid. Enzymatic degradation of PGE2 involves the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). The present study examined a range of normal tissues in the human and mouse and found high levels of 15-PGDH in the large intestine. By contrast, the expression of 15-PGDH is decreased in several colorectal carcinoma cell lines and in other human malignancies such as breast and lung carcinomas. Consistent with these findings, we observe diminished 15-Pgdh expression in ApcMin+/- mouse adenomas. Enzymatic activity of 15-PGDH correlates with expression levels and the genetic disruption of 15-Pgdh completely blocks production of the urinary PGE2 metabolite. Finally, 15-PGDH expression and activity are significantly down-regulated in human colorectal carcinomas relative to matched normal tissue. In summary, these results suggest a novel tumor suppressive role for 15-PGDH due to loss of expression during colorectal tumor progression.

    Original languageEnglish (US)
    Pages (from-to)3217-3223
    Number of pages7
    JournalJournal of Biological Chemistry
    Volume280
    Issue number5
    DOIs
    StatePublished - Feb 4 2005

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Fingerprint Dive into the research topics of '15-hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer'. Together they form a unique fingerprint.

    Cite this