Transgenic Wnt/TCF pathway reporters: all you need is Lef?

Barolo, Scott

doi:10.1038/sj.onc.1210057

Cited by 150 publications

(147 citation statements)

References 63 publications

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“…Multimerized TCF reporter is necessary but may not be sufficient to give a complete and definitive readout of Wnt signaling in vivo (22). The discrepancies between TOPGAL reporter activity and Wnt signaling have been described previously (28,29) and may be due to differences in the regulation of transgene expression in specific tissue contexts. We observed that the Wnt response cells, via either TOPGAL reporter activity or nuclear localization of ␤-catenin, do not completely correlate with mitotic cells.…”

Section: Discussionmentioning

confidence: 99%

R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/β-catenin pathway

Zhao¹,

Kim²,

Vera³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

108

100

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R-Spondin1 (RSpo1) is a novel secreted protein that augments canonical Wnt/␤-catenin signaling. We injected recombinant RSpo1 protein into transgenic Wnt reporter TOPGAL mice and have identified the oral mucosa as a target tissue for RSpo1. Administration of RSpo1 into normal mice triggered nuclear translocation of ␤-catenin and resulted in increased basal layer cellularity, thickened mucosa, and elevated epithelial cell proliferation in tongue. We herein evaluated the therapeutic potential of RSpo1 in treating chemotherapy or radiotherapyinduced oral mucositis in several mouse models. Prophylactic treatment with RSpo1 dose-dependently overcame the reduction of basal layer epithelial cellularity, mucosal thickness, and epithelial cell proliferation in tongues of mice exposed to whole-body irradiation. RSpo1 administration also substantially alleviated tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of tongue ulceration in mice receiving a single fraction, high dose head-only radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and keratinocyte growth factor resulted in complete healing of tongue ulcers in mice subjected to snout-only irradiation. In conclusion, our results demonstrate RSpo1 to be a potent therapeutic agent for oral mucositis by enhancing basal layer epithelial regeneration and accelerating mucosal repair through upregulation of Wnt/␤-catenin pathway.RSpo1 ͉ tongue ulceration ͉ head-only radiation ͉ TOPGAL ͉ 5-FU

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Section: Discussionmentioning

confidence: 99%

R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/β-catenin pathway

Zhao¹,

Kim²,

Vera³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

108

100

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“…Several studies of different TCFs largely agree that CCTTTGAT is a high affinity site for the HMG domain (Barolo 2006 TCF can also bind motifs differing from this consensus (Hallikas et al 2006). In addition, several Wnt response elements (WREs) in flies have functional TCF-binding sites varying significantly from the consensus (Chang et al 2008a;Lee and Frasch 2000;Riese et al 1997).…”

Section: Into the Nucleus-target Gene Regulation By Bcat/armmentioning

confidence: 99%

Wnt Signaling from Development to Disease: Insights from Model Systems

Cadigan¹,

Peifer²

2009

Cold Spring Harbor Perspectives in Biology

275

259

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One of the early surprises in the study of cell adhesion was the discovery that b-catenin plays dual roles, serving as an essential component of cadherin-based cell -cell adherens junctions and also serving as the key regulated effector of the Wnt signaling pathway. Here, we review our current model of Wnt signaling and discuss how recent work using model organisms has advanced our understanding of the roles Wnt signaling plays in both normal development and in disease. These data help flesh out the mechanisms of signaling from the membrane to the nucleus, revealing new protein players and providing novel information about known components of the pathway.

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“…The TOPFLASH plasmid contains three LEF/TCF binding sites (17). In order to establish a Wnt/β-catenin signaling-response stable cell line for drug screening, we amplified the TOP element that contained three LEF/TCF binding sites from TOPFLASH and inserted them into the pGL4.3 reporter plasmid that contains a hygromycin B phosphotransferase coding gene (Hygr) and a luciferase reporter gene.…”

Section: Generation Of the Hek 293-top/fop Stable Cell Lines For Drugmentioning

confidence: 99%

Evaluation of anti-Wnt/β-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system

Chuang

Lieu

Tsai

et al. 2010

Braz J Med Biol Res

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Transgenic Wnt/TCF pathway reporters: all you need is Lef?

Cited by 150 publications

References 63 publications

R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/β-catenin pathway

R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/β-catenin pathway

Wnt Signaling from Development to Disease: Insights from Model Systems

Evaluation of anti-Wnt/β-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system

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