title: EGCG inhibits recepteur d'origine nantais expression by suppressing             Egr-1 in gastric cancer cells.
abstract: Abnormal accumulation and activation of the recepteur d'origine nantais (RON) has been implicated in epithelial tumor carcinogenesis. In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the induction of RON and tumor growth in human gastric cancer. EGCG inhibited phorbol 12-myristate 13-acetate (PMA)-induced RON expression and reduced RON transcriptional activity. However, (-)-epigalloca-techin (EGC), (-)-epicatechin gallate (ECG) and (-)‑epicatechin (EC) did not affect RON expression. Experiments with deleted and site-directed mutagenesis of the RON promoter indicated that Egr-1 binding sites in the RON promoter may be the EGCG‑response element acting as a cis-element in gastric cancer cells. EGCG also inhibited PMA-induced Egr-1 expression and DNA binding in a dose-dependent manner. Furthermore, gastric cancer cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by EGCG and siRNA-targeted RON and Egr-1. EGCG significantly reduced tumor growth in an in vivo tumor model, whereas RON expression was downregulated. These results suggest that EGCG may exert at least part of its anticancer effect by controlling RON expression through suppression of Egr-1 activation.
authors: Research Institute of Medical Sciences, Chonnam National University                     Medical School, Gwangju, Republic of Korea.
authors: Jung Sun
authors: JS
authors: Park
authors: Pham Ngoc
authors: PN
authors: Khoi
authors: Young Eun
authors: YE
authors: Joo
authors: Young Han
authors: YH
authors: Lee
authors: Sven A
authors: SA
authors: Lang
authors: Oliver
authors: O
authors: Stoeltzing
authors: Young Do
authors: YD
authors: Jung
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010936:Plant Extracts; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism*; D013662:Tea; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D010936:Plant Extracts; D034741:RNA, Small Interfering; D013662:Tea; C016658:phorbolol myristate acetate; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; C057580:gallocatechol; D013755:Tetradecanoylphorbol Acetate