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

Abstract:

:Functional activation of beta-catenin/Tcf signaling plays an important role in the early events in colorectal carcinogenesis. We examined the effect of ionomycin against beta-catenin/Tcf signaling in colon cancer cells. Reporter gene assay showed that ionomycin inhibited beta-catenin/Tcf signaling efficiently. In addition, the inhibition of beta-catenin/Tcf signaling by ionomycin in HEK293 cells transiently transfected with a constitutively mutant beta-catenin gene, whose product is not phosphorylated by GSK3beta, indicates that its inhibitory mechanism is related to beta-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 beta-catenin and Tcf-4 is disrupted and the amount of beta-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 beta-catenin/Tcf signaling in colon cancer cells and its inhibitory mechanism is related to the decreased nuclear beta-catenin products and to the suppressed binding of Tcf complexes to consensus DNA.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Park CH,Hahm ER,Lee JH,Jung KC,Rhee HS,Yang CH

doi

10.1093/carcin/bgi145

keywords:

subject

Has Abstract

pub_date

2005-11-01 00:00:00

pages

1929-33

issue

11

eissn

0143-3334

issn

1460-2180

pii

bgi145

journal_volume

26

pub_type

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