title: Inhibition of beta-catenin-mediated transactivation by flavanone in AGS gastric cancer cells.
abstract: 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 GSK3beta, 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.
authors.affiliation: Division of Chemistry and Molecular Engineering, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Chi Hoon
authors.initials: CH
authors.lastname: Park
authors.forename: Eun Ryeong
authors.initials: ER
authors.lastname: Hahm
authors.forename: Ju Hyung
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung Chae
authors.initials: KC
authors.lastname: Jung
authors.forename: Chul Hak
authors.initials: CH
authors.lastname: Yang
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D015342:DNA Probes; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015342:DNA Probes; D044950:Flavanones; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; C028610:flavanone