Carcinogenesis, Vol. 20, No. 4, 737-740,
April 1999
© 1999 Oxford University Press
Short Communications |
Differential expression of prostaglandin endoperoxide H synthase-2 and formation of activated ß-catenin–LEF-1 transcription complex in mouse colonic epithelial cells contrasting in Apc
Laboratory of Nutritional and Molecular Regulation, Division of Basic Sciences, National Cancer Institute and
1 Intramural Research Support Program, SAIC–Frederick, NCI–FCRDC, Frederick, MD 21702, USA
Mutations in Apc underlie the intestinal lesions in familial adenomatous polyposis and are found in >85% of sporadic colon cancers. They are frequently associated with overexpression of prostaglandin endoperoxide H synthase-2 (PGHS-2) in colonic adenomas. It has been suggested that Apc mutations are linked mechanistically to increased PGHS-2 expression by elevated nuclear accumulation of ß-catenin–Tcf-LEF transcription complex. In the present study, we show that PGHS-2 is differentially expressed in mouse colonic epithelial cells with distinct Apc status. Cells with a mutated Apc expressed markedly higher levels of PGHS-2 mRNA and protein and produced significantly more prostaglandin E2 than cells with normal Apc. Using electrophoretic mobility shift assays, we demonstrate that DNA–ß-catenin–LEF-1 complex formation is differentially induced in these two cell lines in an Apc-dependent manner. Our data indicate that the differential induction of ß-catenin–LEF-1 complex correlates closely with differential expression of PGHS-2. These findings support the hypothesis that the differential expression of PGHS-2 is mediated through the proposed ß-catenin/Tcf-LEF signaling pathway.
Abbreviations: APC, adenomatous polyposis coli; IFN
, interferon-; LPS, lipopolysaccharide; PGE2, prostaglandin E2; PGHS-2, prostaglandin endoperoxide H synthase-2.
2 Present address: Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA
3 To whom correspondence should be addressedEmail: phang{at}mail.ncifcrf.gov
* These two authors contributed equally to this study
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