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Gene Review:

Hpgd - hydroxyprostaglandin dehydrogenase 15 (NAD)

Mus musculus

Synonyms: 15-PGDH, AV026552, Pgdh1, Prostaglandin dehydrogenase 1

Backlund, M.G. et al., Ding, Y. et al., Matsuo, M. et al., Rodriguez, M. et al., Zhou, H. et al., et al.

Rodriguez, Clare-Salzler,

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Disease relevance of Hpgd

In summary, these results suggest a novel tumor suppressive role for 15-PGDH due to loss of expression during colorectal tumor progression [1].
Consistent with these findings, we observe diminished 15-Pgdh expression in ApcMin+/- mouse adenomas [1].
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 [1].
NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer [2].
The mouse NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) gene and its 5'-flanking region was cloned from a 129 mouse ES bacteriophage P1 genomic library [3].

High impact information on Hpgd

Enzymatic activity of 15-PGDH correlates with expression levels and the genetic disruption of 15-Pgdh completely blocks production of the urinary PGE2 metabolite [1].
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 [1].
These results suggest that 15-PGDH may decrease the level of proliferative PGE2, induce apoptosis and function like a tumor suppressor [2].
Using quantitative reverse transcription-polymerase chain reaction, we analyzed RNA levels of the key prostaglandin catabolic enzyme, NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH), in 19 pairs of NSCLC tumors and adjacent non-malignant tissue from the same patient [2].
This suggests that the increased expression of COX-2 and PGE synthase in tumors may work in concert with the decreased expression of 15-PGDH to amplify an increase in tissue levels of proliferative PGE2 [2].

Biological context of Hpgd

The cDNA contains a 798 bp open reading frame that codes for a protein of 266 amino acids (M(r) 28775) which shares 87% identity with the human 15-PGDH protein [4].
The cDNA for mouse NAD+ dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) was isolated from a lung cDNA library [4].

Associations of Hpgd with chemical compounds

Enzymatic degradation of PGE2 involves the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) [1].
The enhanced proinflammatory eicosanoids is secondary to increased cyclooxygenase-2 (Cox-2) expression and low levels of prostaglandin/leukotriene catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) [5].
NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the oxidation of the 15(S) hydroxyl group of prostaglandins to a 15-keto group resulting in a significant reduction of the biological activities of prostaglandins [6].

Other interactions of Hpgd

Eicosanoid Imbalance in the NOD Mouse Is Related to a Dysregulation in Soluble Epoxide Hydrolase and 15-PGDH Expression [5].

Analytical, diagnostic and therapeutic context of Hpgd

Northern blot analysis demonstrated that 15-PGDH mRNA is expressed primarily in lung, intestine, stomach and liver [4].

References

15-Hydroxyprostaglandin dehydrogenase is down-regulated in colorectal cancer. Backlund, M.G., Mann, J.R., Holla, V.R., Buchanan, F.G., Tai, H.H., Musiek, E.S., Milne, G.L., Katkuri, S., DuBois, R.N. J. Biol. Chem. (2005) [Pubmed]
NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. Ding, Y., Tong, M., Liu, S., Moscow, J.A., Tai, H.H. Carcinogenesis (2005) [Pubmed]
Characterization of the genomic structure and promoter of the mouse NAD+-dependent 15-hydroxyprostaglandin dehydrogenase gene. Matsuo, M., Ensor, C.M., Tai, H.H. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
Cloning and expression of the cDNA for mouse NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase. Matsuo, M., Ensor, C.M., Tai, H.H. Biochim. Biophys. Acta (1996) [Pubmed]
Eicosanoid Imbalance in the NOD Mouse Is Related to a Dysregulation in Soluble Epoxide Hydrolase and 15-PGDH Expression. Rodriguez, M., Clare-Salzler, M. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
C-Terminal region of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase is involved in the interaction with prostaglandin substrates. Zhou, H., Yan, F., Tai, H.H. Eur. J. Biochem. (2001) [Pubmed]

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