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: UMLS:C0023890 (
cirrhosis
)
42,195
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cyclooxygenase-2 (COX-2), a rate limiting step in arachidonic acid cascade, plays a key role in the biosynthesis of prostaglandin E2 (PGE2) upon inflammatory stimuli, growth factors, hormones and other cellular stresses. Overproduction of PGE2 stimulates proliferation of various cancer cells, confers resistance to apoptosis and favors metastasis and angiogenesis. The steady-state level of PGE2 is maintained by interplay between the biosynthetic pathway including COX and PGE2 synthases and the catabolic pathways involving nicotinamide adenine dinucleotide (NAD(+))-dependent
15-hydroxyprostaglandin dehydrogenase
(
15-PGDH
).
15-PGDH
is a crucial enzyme responsible for the biological inactivation of PGE2. Adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory factors used. COX-2 is induced in hepatocytes after partial hepatectomy (PH), in animal models of
cirrhosis
, in human hepatoma cell lines, in human HCC and after HBV and HCV infection. However, no data are available regarding
15-PGDH
expression in HCC. Our results show that
15-PGDH
is downregulated in human hepatoma cells with a high COX-2 expression, in chemical and genetic murine models of HCC and in human HCC biopsies. Moreover,
15-PGDH
expression is suppressed by EGF (epidermal growth factor) and HGF (hepatocyte growth factor) mainly involving PI3K (phosphatidylinositol-3-kinase), ERK (extracellular signal-regulated kinase) and p38MAPK (mitogen-activated protein kinase) activation. Conversely, ectopic expression of
15-PGDH
induces apoptosis in hepatoma cells and decreases the growth of hepatoma cells in nude mice whereas the silencing of
15-PGDH
increases the tumor formation. These data suggest a potential therapeutic application of
15-PGDH
in HCC.
...
PMID:Regulation of 15-hydroxyprostaglandin dehydrogenase expression in hepatocellular carcinoma. 2395 7
