Although its role in the suppression of colon tumorigenesis has been well learned, little is known about the role of 15-PGDH in the process of tumor metastasis.
Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer.
Recently, 15-hydroxyprostaglandin dehydrogenase [NAD+] (15-PGDH), the key enzyme in prostaglandin degradation, was found to be down-regulated in human gastric cancer tissues, but little is known about its role in gastric tumorigenesis.
Susceptibility to AOM-induced tumorigenesis is mediated by a marked induction of dysplasia, proliferation, and cyclin D1 expression throughout microscopic aberrant crypt foci arising in 15-PGDH null colons and is concomitant with a doubling of prostaglandin E(2) in 15-PGDH null colonic mucosa.
The recently identified colorectal tumour suppressor 15-prostaglandin dehydrogenase (15-PGDH) catalyses prostaglandin turnover and is downregulated at a very early stage in colorectal tumorigenesis; however, the mechanism responsible remains unclear.
These findings indicated that COX-2 and 15-PGDH, the two enzymes that regulate PGE<sub>2</sub> levels, were significantly altered in gastric cancer, and that <i>H. pylori</i> may contribute to gastric carcinogenesis through modulating COX-2 and 15-PGDH mRNA expression and protein synthesis.
We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic submucosal dissection (ESD) and gastric cancer cell lines.