RGD Reference Report - Loss of 15-Hydroxyprostaglandin Dehydrogenase Increases Prostaglandin E2 in Pancreatic Tumors. - Rat Genome Database

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Loss of 15-Hydroxyprostaglandin Dehydrogenase Increases Prostaglandin E2 in Pancreatic Tumors.

Authors: Pham, H  Chen, M  Li, A  King, J  Angst, E  Dawson, DW  Park, J  Reber, HA  Hines, OJ  Eibl, G 
Citation: Pham H, etal., Pancreas. 2009 Oct 7.
RGD ID: 2317179
Pubmed: PMID:19820419   (View Abstract at PubMed)
PMCID: PMC2859226   (View Article at PubMed Central)
DOI: DOI:10.1097/MPA.0b013e3181baecbe   (Journal Full-text)

OBJECTIVES:: Prostaglandin E2 (PGE2) is a product of cyclooxygenase (COX) and PGE synthase (PGES) and deactivated by 15-hydroxyprostaglandin dehydrogenase (PGDH). Down-regulation of PGDH contributes to PGE2 accumulation in lung and colon cancers but has not been identified in pancreatic cancer. METHODS:: Normal human pancreatic and tumor-matched tissues, as well as MiaPaCa-2 and BxPC-3 cell lines, were assessed for COX-2, microsomal PGES-1, PGDH, and snail homolog 1 (SNAI1) and SNAI2 expressions by real-time polymerase chain reaction and Western blotting and PGE2 by enzyme-linked immunosorbent assay. RESULTS:: Normal tissues exhibited low COX-2 messenger RNA (mRNA) and protein expressions and high PGDH mRNA and protein expressions and PGE2 levels at 13 pg/mg of protein. In contrast, tumor tissues exhibited high COX-2 mRNA and protein expressions and low PGDH mRNA and protein expressions and PGE2 levels at 32 pg/mg of protein. Tumor tissues exhibited significantly elevated expressions of SNAI2 mRNA and protein but not SNAI1 because SNAI1 and SNAI2 reportedly down-regulate PGDH expression. The COX-2-positive BxPC-3 but not the COX-2-negative MiaPaCa-2 treated with 100-nmol/L PGE2 induced phosphorylated extracellular signal-related kinase that was blocked by the mitogen-activated protein kinase kinase inhibitor U0126, demonstrating the ability of PGE2 to activate ERK. CONCLUSIONS:: These results suggest that enhanced PGE2 production proceeds through the expressions of COX-2 and microsomal PGES-1 and down-regulation of PGDH by SNAI2 in pancreatic tumors.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pancreatic cancer  IEP 2317179mRNA and protein:increased expression:pancreasRGD 
pancreatic cancer  ISOPTGS2 (Homo sapiens)2317179; 2317179mRNA and protein:increased expression:pancreasRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information