Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.36 (
hyaluronidase
)
4,606
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
It has been reported that two inducible prostaglandin synthetic enzymes, cylooxygenase-2 (COX-2) and microsomal PGE synthase, are over-expressed in non-small cell lung cancer (NSCLC). 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. We found that 100% of tumor-tissue pairs showed at least a 2-fold decrease and 61% showed a 10-fold decrease. 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. To further explore if
15-PGDH
is related to tumorigenesis, athymic nude mice were injected with control A549 cells or cells transiently over-expressing wild-type or mutant
15-PGDH
(Y151F). It was found that mice injected with control A549 cells or with cells expressing mutant enzyme produced tumors normally. However, mice injected with A549 cells expressing wild-type
15-PGDH
had a significant decrease in tumor growth. Examining the effects of
15-PGDH
expression on cellular changes in A549 cells, we found that over-expression of
15-PGDH
induced apoptosis of A549 cells as evidenced by fragmentation of DNA, activation of pro-caspase 3, cleavage of poly(ADP-ribose) polymerase and decreased expression of Bcl-2. We also found that the expression of
15-PGDH
was negatively related to that of pro-adhesive and invasive CD44. Furthermore, the expression of
15-PGDH
was found to be stimulated by
hyaluronidase
. These results suggest that
15-PGDH
may decrease the level of proliferative PGE2, induce apoptosis and function like a tumor suppressor.
...
PMID:NAD+-linked 15-hydroxyprostaglandin dehydrogenase (15-PGDH) behaves as a tumor suppressor in lung cancer. 1535 36
