Unique Effects of Wnt Signaling on Prostate Cancer Cells: Modulation of the Androgen Signaling Pathway by Interactions of the Androgen Receptor Gene and Protein with Key Components of the Canonical Wnt Signaling Pathway

  • Matthew J. Tanner
  • Elina Levina
  • Michael Shtutman
  • Mengqian Chen
  • Patrice Ohouo
  • Ralph Buttyan


Canonical Wnt is a ligand-driven signaling pathway that augments the intracellular stability of β-catenin. β-Catenin is transcriptional coactivator protein that is best known for its role in regulating the activity of the Tcf/LEF-1 transcription factor family but it binds and regulates several other types of transcription factors including the androgen receptor (AR). Aberrant Wnt signaling can contribute to oncogenesis and this is often a factor in human colon cancer where mutations in key Wnt regulatory genes promote constitutive β-catenin stabilization in the tumor cells. This chapter reviews the evidence that Wnt signaling might also play some role in prostate cancer through its effects on the expression of androgen-dependent genes. These effects are mechanistically driven through a diverse set of interactions between three key molecules in the Wnt pathway, β-catenin, glycogen synthase kinase-3β, and Tcf/LEF-1, with the human AR gene and protein. For the most part, these interactions enhance AR expression or its functional activity as a transcription factor and they have the potential of augmenting the growth of prostate cancer cells even when androgen levels are within castrate range. Although the common gene mutations that drive abnormal Wnt signaling in other human cancers are not as frequently observed in human prostate tumors, gene expression profiles of prostate tumors often show overexpression of wnt ligands in the cancer cells and this may have a comparable effect on prostate cancer development or progression. Given the important role of the canonical Wnt signaling pathway in promoting oncogenesis in some human tissues as well as the specific involvement of key Wnt molecules in regulating androgen action in prostate cancer cells, effectors of the Wnt signaling pathway likely represent unique targets to bring metastatic and castration-resistant prostate cancers under control.


Androgen Receptor Prostate Cancer Cell Prostate Epithelial Cell Androgen Receptor Protein Androgen Signaling 


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Matthew J. Tanner
  • Elina Levina
  • Michael Shtutman
  • Mengqian Chen
  • Patrice Ohouo
  • Ralph Buttyan
    • 1
  1. 1.The Division of UrologyAlbany College of MedicineAlbanyUSA

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