Wednesday, July 17th, 2019


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The Roles of Notch and Wnt Signaling Pathways in the Pathogenesis of Wilms Tumor
Authors:  Ting Li, Ph.D., Tianqi Zhu, Ph.D., M.D., Xiaojuan Wu, Ph.D., M.D., Jixin Yang, Ph.D., M.D., and Bin Yi, Ph.D., M.D.
  Objective: To assess the expression of Notch and Wnt signaling pathway genes/proteins and the cooperative involvement of these pathways in the pathogenesis of Wilms tumor (WT).
Study Design:
WT tissues and nonneoplastic renal tissues were collected, and the mRNA and protein expression of Notch1 and vascular endothelial growth factor (VEGF) were determined by real-time PCR and immunohistochemistry. In addition, the expression of Notch and Wnt signaling pathway factors were measured by Western blot analysis in a human nephroblastoma cell line (SK-NEP-1) treated with a Notch inhibitor, DAPT.
Immunohistochemical staining revealed that Notch1 and VEGF were significantly increased in the WT group, and its expression was positively correlated with the tumor stage. Notch1 and VEGF mRNA expression in the WT group was also significantly higher than that in the control group. The expression levels of Notch1 and Jagged1 were significantly decreased after treating with 10 μM DAPT. Moreover, the expression levels of Wnt1, VEGF, and β-catenin were significantly decreased after treating with 10 μM DAPT.
The Notch and Wnt signaling pathways may play a cooperative role in WT pathogenesis, and the inhibition of Wnt signaling pathway and the downregulation of VEGF would exist after inhibiting the Notch signaling pathway.
Keywords:  nephroblastoma, Notch pathway, Notch proteins, Notch receptors, pathogenesis, VEGF, vascular endothelial growth factor, Wilms tumor, Wilms’ tumor, Wnt pathway
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