Prostaglandin H synthase 2 is expressed abnormally in human colon cancer: evidence for a transcriptional effect.

W Kutchera, DA Jones, N Matsunami… - Proceedings of the …, 1996 - National Acad Sciences
W Kutchera, DA Jones, N Matsunami, J Groden, TM McIntyre, GA Zimmerman, RL White…
Proceedings of the National Academy of Sciences, 1996National Acad Sciences
Evidence from epidemiological studies, clinical trials, and animal experiments indicates that
inhibitors of prostaglandin synthesis lower the risk of colon cancer. We tested the hypothesis
that abnormal expression of prostaglandin H synthase 2 (PHS-2), which can be induced by
oncogenes and tumor promoters, occurs during colon carcinogenesis by examining its level
in colon tumors. Human colon cancers were found to have an increased expression of PHS-
2 mRNA compared with normal colon specimens from the same patient (n= 5). In situ …
Evidence from epidemiological studies, clinical trials, and animal experiments indicates that inhibitors of prostaglandin synthesis lower the risk of colon cancer. We tested the hypothesis that abnormal expression of prostaglandin H synthase 2 (PHS-2), which can be induced by oncogenes and tumor promoters, occurs during colon carcinogenesis by examining its level in colon tumors. Human colon cancers were found to have an increased expression of PHS-2 mRNA compared with normal colon specimens from the same patient (n = 5). In situ hybridization showed that the neoplastic colonocytes had increased expression of PHS-2 (n = 4). Additionally, five colon cancer cell lines were shown to express high levels of PHS-2 mRNA even in the absence of a known inducer of PHS-2. To study the basis for this increased gene expression, we transfected a colon cancer cell line, HCT-116, with a reporter gene containing 2.0 kb of the 5' regulatory sequence of the PHS-2 gene. Constitutive transcription of the reporter gene was observed, whereas normal control cell lines transcribed the reporter only in response to an exogenous agonist. We conclude that PHS-2 is transcribed abnormally in human colon cancers and that this may be one mechanism by which prostaglandins or related compounds that support carcinogenesis are generated.
National Acad Sciences