Inhibition of {beta}-catenin-mediated transactivation by flavanone in AGS gastric cancer cells
- Division of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742 (Korea, Republic of)
Recently, data which prove that Wnt pathway activation may be an early event in multistep carcinogenesis in the stomach have been accumulating. We examined the effect of flavanone against {beta}-catenin/Tcf signaling in AGS gastric cancer cells. Reporter gene assay showed that flavanone inhibited {beta}-catenin/Tcf signaling efficiently. In addition, the inhibition of {beta}-catenin/Tcf signaling by flavanone in HEK293 cells transiently transfected with constitutively mutant {beta}-catenin gene, whose product is not phosphorylated by GSK3{beta}, indicates that its inhibitory mechanism was related to {beta}-catenin itself or downstream components. To investigate the precise inhibitory mechanism, we performed immunofluorescence, Western blot, and EMSA. As a result, our data revealed that there is no change of {beta}-catenin distribution and of nuclear {beta}-catenin levels through flavanone. In addition, the binding of Tcf complexes to DNA is not influenced by flavanone. The {beta}-catenin/Tcf transcriptional target gene cyclinD1 was downregulated by flavanone. These data suggest that flavanone inhibits the transcription of {beta}-catenin/Tcf responsive genes, by modulating Tcf activity without disrupting {beta}-catenin/Tcf complex formation.
- OSTI ID:
- 20710807
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 331, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2005.03.242; PII: S0006-291X(05)00720-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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