Journal Article

Differential expression of prostaglandin endoperoxide H synthase-2 and formation of activated β-catenin–LEF-1 transcription complex in mouse colonic epithelial cells contrasting in <i>Apc</i>

J.M. Mei, N.G. Hord, D.F. Winterstein, S.P. Donald and J.M. Phang

in Carcinogenesis

Volume 20, issue 4, pages 737-740
Published in print April 1999 | ISSN: 0143-3334
Published online April 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.4.737
Differential expression of prostaglandin endoperoxide H synthase-2 and formation of activated β-catenin–LEF-1 transcription complex in mouse colonic epithelial cells contrasting in Apc

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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 β-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–β-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 β-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 β-catenin/Tcf-LEF signaling pathway.

Keywords: APC, adenomatous polyposis coli; IFNγ, interferon-γ; LPS, lipopolysaccharide; PGE2, prostaglandin E2; PGHS-2, prostaglandin endoperoxide H synthase-2.

Journal Article.  2847 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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