Journal Article

Ionomycin downregulates β-catenin/Tcf signaling in colon cancer cell line

Chi Hoon Park, Eun Ryeong Hahm, Ju Hyung Lee, Kyung Chae Jung, Ho Sung Rhee and Chul Hak Yang

in Carcinogenesis

Volume 26, issue 11, pages 1929-1933
Published in print November 2005 | ISSN: 0143-3334
Published online June 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi145
Ionomycin downregulates β-catenin/Tcf signaling in colon cancer cell line

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Functional activation of β-catenin/Tcf signaling plays an important role in the early events in colorectal carcinogenesis. We examined the effect of ionomycin against β-catenin/Tcf signaling in colon cancer cells. Reporter gene assay showed that ionomycin inhibited β-catenin/Tcf signaling efficiently. In addition, the inhibition of β-catenin/Tcf signaling by ionomycin in HEK293 cells transiently transfected with a constitutively mutant β-catenin gene, whose product is not phosphorylated by GSK3β, indicates that its inhibitory mechanism is related to β-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunoprecipitation analysis, western blot and electrophoretic mobility shift assay. As a result, our data reveal that the association of β-catenin and Tcf-4 is disrupted and the amount of β-catenin product in the nucleus is decreased by ionomycin in a concentration-dependent manner. Moreover, ionomycin strongly suppressed the binding of the Tcf complexes to its specific DNA-binding sites. The significance of the current work is that ionomycin is a negative regulator of β-catenin/Tcf signaling in colon cancer cells and its inhibitory mechanism is related to the decreased nuclear β-catenin products and to the suppressed binding of Tcf complexes to consensus DNA.

Keywords: APC, axin-adenomatous polyposis coli; CRC, colorectal cancer cell; EMSA, electrophoretic mobility shift assay; GSK3β, glycogen synthase kinase 3β; TRE, Tcf response elements

Journal Article.  4564 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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