We investigated the expression and regulation of 15-PGDH in eary gastric carcinogenesis utilizing endoscopic submucosal dissection (ESD) and gastric cancer cell lines.
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.
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.
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.
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.
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.
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.