title: Enhancement of GLI1-transcriptional activity by beta-catenin in human cancer cells.
abstract: The Hedgehog (Hh) signaling pathway and the Wnt signaling pathway are known to play important roles in carcinogenesis and the progression of various human malignant tumors. Although a relationship between these two pathways has recently been reported, the mechanism by which beta-catenin, one of the key molecules of the Wnt signaling pathway, influences the Hh pathway has not yet been revealed in detail. To clarify the role of beta-catenin in relation to the Hh signaling pathway, we transfected GLI1 and beta-catenin expression constructs into human malignant cells, including stomach, colon, and lung cancers, and evaluated the luciferase activity of GLI-responsive reporter constructs. While exogenous GLI1 increased the luciferase activity, exogenous beta-catenin also enhanced the activity under overexpression of GLI1. However, co-transfection with T-cell factor (TCF)-4 or lymphocyte enhancer factor (LEF)-1 did not influence the activity, indicating that the enhancement of beta-catenin in relation to the Hh signaling pathway is not TCF/LEF-dependent. Our results suggest that beta-catenin might be involved in the Hh signaling pathway via enhancement of the transcriptional activity of GLI.
authors.affiliation: Department of Gastroenterology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.forename: Masashi
authors.initials: M
authors.lastname: Kondo
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Usami
authors.forename: Takayuki
authors.initials: T
authors.lastname: Fukui
authors.forename: Kaoru
authors.initials: K
authors.lastname: Shimokata
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ando
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sekido
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D053823:Hedgehog Proteins; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D015513:Oncogene Proteins; D051820:TCF Transcription Factors; D015534:Trans-Activators; D051153:Wnt Proteins; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin; D008156:Luciferases