XB-IMG-159438
Xenbase Image ID: 159438
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Figure 1. Different Sox factors are antagonists or agonists of the canonical Wnt pathway and are expressed in the normal and neoplastic gut. (A) Effect of different Sox family members on Wnt signaling activity. 293T cells (shown) and COS cells (not shown) were transfected with Sox2, Sox3, Sox4, Sox5, Sox6, Sox7, Sox9, Sox10, Sox11, Sox17, and Sox18 together with a TCF-luciferase reporter plasmid (TOP-flash) and an expression plasmid encoding a stabilized form of β-catenin (carrying the S37A mutation). Transfection with β-catenin(S37A) alone resulted in significant activation of the reporter plasmid. Sox2, Sox3, Sox7, Sox9, Sox10, and Sox17 repressed the β-catenin-mediated activation of TOP-flash, whereas Sox4, Sox5, and Sox11 enhanced β-catenin/Wnt activity. Data are shown as ratios of the activity in cotransfected cells to the activity in cells transfected with β-catenin(S37A) alone. Transfection with Sox factors without β-catenin(S37A) did not result in significant TOP-flash activity (data not shown). Letters above the bars denote the Sox subfamily. Error bars indicate standard errors of the means for replicate samples from two separate experiments. −, absent; +, present. (B) Analysis of published microarray data (8, 32, 38). The expression levels of the Wnt antagonists Dkk and Sox17 were reduced in seven of eight tumor samples relative to those in the normal gut samples. The levels of expression of several pro-Wnt signaling genes, Sox4, TCF4, and LEF1, and the Wnt target gene cyclin D1 (CCND1) were elevated in tumor samples relative to those in normal gut samples. The color scale for normalized transcript levels is as follows: red, high; yellow, moderate; and blue, low. (C) Sox4 and Sox17 proteins are expressed in the normal gut epithelium and in APCmin/+ tumors. In the small intestine, Sox17 and Sox4 proteins (green) are expressed in the nuclei of the epithelial cells (a duodenum sample is shown). The Sox4 expression domain is located predominantly in the crypt, whereas Sox17 protein is found throughout the crypt and villus. The right panels show adjacent sections from APCmin/+ tumors in which Sox17 and Sox4 proteins appear to be in mutually exclusive domains. Nuclei are stained with the red nuclear dye PoPro3. Scale bars in duodenum panels, 50 μm. Image published in: Sinner D et al. (2007) Copyright © 2007. Image reproduced with permission of the Publisher, American Society for Cell Biology (ASCB). This is an Open Access article. Larger Image Printer Friendly View |