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Publication : Activation of Wnt/beta-catenin/Tcf signaling in mouse skin carcinogenesis.

First Author  Bhatia N Year  2005
Journal  Mol Carcinog Volume  42
Issue  4 Pages  213-21
PubMed ID  15765534 Mgi Jnum  J:97893
Mgi Id  MGI:3576576 Doi  10.1002/mc.20077
Citation  Bhatia N, et al. (2005) Activation of Wnt/beta-catenin/Tcf signaling in mouse skin carcinogenesis. Mol Carcinog 42(4):213-21
abstractText  Although Wnt/beta-catenin/Tcf signaling pathway has been shown to be an important factor in the development of many malignancies including colorectal, ovarian, prostate, and many other cancers, little is known about its role in non-melanoma skin cancers. Here, we report the first evidence that beta-catenin/Tcf signaling pathway is constitutively activated in non-melanocytic skin tumors induced by two stage chemical carcinogenesis protocol. Mouse skin tumors showed cytoplasmic and nuclear accumulation of beta-catenin, and upregulation of beta-catenin/Tcf target genes (c-myc and c-jun). We found high levels of skin-expressed Wnt proteins (Wnt 3, 4, and 10b) in different parts of the tumors, likely representing key upstream events in beta-catenin/Tcf activation during mouse skin carcinogenesis. Inhibition of beta-catenin/Tcf signaling by ectopic expression of dominant negative Tcf4 resulted in significant inhibition of growth in squamous cell carcinoma cells. A role of the constitutive activation of beta-catenin/Tcf signaling in skin carcinogenesis is discussed.
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