WNT SIGNALING IN PROSTATE DEVELOPMENT AND CARCINOGENESIS

Gvantsa Kharaishvili,Katerina Trtkova,Zdenek Kolar,Dana Simkova,Eka Makharoblidze,Jan Bouchal

doi:10.5507/bp.2011.016

Abstract

The Wnt signaling pathway is crucial for cell fate decisions, stem cell renewal, regulation of cell proliferation and differentiation. Deregulated Wnt signaling is also implicated in a number of hereditary and degenerative diseases and cancer. This review highlights the role of the Wnt pathway in the regulation of stem/progenitor cell renewal and prostate gland development and how this signaling is altered in prostate cancer. Recent evidence suggests that Wnt signaling regulates androgen activity in prostate cancer cells, enhances androgen receptor expression and promotes the growth of prostate cancer even after androgen ablation therapy. There is also strong evidence that Wnt signaling is enhanced in androgen-ablation resistant tumors and bone metastases. Further study of the modulators of this pathway will be of therapeutic relevance as inhibition of Wnt signaling may have the potential to reduce the self-renewal and aggressive behaviour of prostate cancer while Wnt signaling activation might enhance stem cell activity when tissue regeneration is required.

Highlights

The Wnt signaling pathway is crucial in a variety of biological processes including cell fate decisions, neural patterning, planar cell polarity, stem cell self-renewal, cell proliferation, differentiation, migration and apoptosis[1,2]
This review focuses on normal prostate development and, normal and cancer stem cells
The term Wnt derives from a contraction of the gene name Wingless, first identified in the development of the fruit fly Drosophila, and the proto-oncogene Int-1 (Integration 1) which was first isolated in mammary tumor models in the mouse[13]

Summary

Methods and results

This review highlights the role of the Wnt pathway in the regulation of stem/progenitor cell renewal and prostate gland development and how this signaling is altered in prostate cancer. Recent evidence suggests that Wnt signaling regulates androgen activity in prostate cancer cells, enhances androgen receptor expression and promotes the growth of prostate cancer even after androgen ablation therapy. There is strong evidence that Wnt signaling is enhanced in androgen-ablation resistant tumors and bone metastases

Conclusions

INTRODUCTION

Findings

CONCLUSION