Maeda Osamu, Kondo Masashi, Fujita Takayoshi, Usami Noriyasu, Fukui Takayuki, Shimokata Kaoru, Ando Takafumi, Goto Hidemi, Sekido Yoshitaka
Department of Gastroenterology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Oncol Rep. 2006 Jul;16(1):91-6.
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.
已知刺猬索尼克（Hh）信号通路和Wnt信号通路在各种人类恶性肿瘤的发生和进展中发挥重要作用。尽管最近报道了这两条通路之间的关系，但Wnt信号通路的关键分子之一β-连环蛋白影响Hh通路的机制尚未详细阐明。为了阐明β-连环蛋白在Hh信号通路中的作用，我们将GLI1和β-连环蛋白表达构建体转染到包括胃癌、结肠癌和肺癌在内的人类恶性细胞中，并评估GLI反应性报告基因构建体的荧光素酶活性。虽然外源性GLI1增加了荧光素酶活性，但外源性β-连环蛋白在GLI1过表达的情况下也增强了活性。然而，与T细胞因子（TCF）-4或淋巴细胞增强因子（LEF）-1共转染并不影响活性，这表明β-连环蛋白与Hh信号通路的增强不依赖于TCF/LEF。我们的结果表明，β-连环蛋白可能通过增强GLI的转录活性参与Hh信号通路。
