Differential Expression of Epithelial and Mesenchymal Proteins in a Panel of Prostate Cancer Cell Lines

Purpose: Epithelial to mesenchymal transition is an important process that results in increased cell migration, invasion and metastasis of many carcinomas. During epithelial to mesenchymal transition epithelial cells down-regulate cell-cell adhesion molecules (ie E-cadherin), up-regulate mesenchymal proteins (ie N-cadherin and cadherin-11), alter polarity, reorganize the cytoskeleton and become isolated. In combination this leads to greater motility. We investigated the role of E-cadherin and the associated catenin-protein complex in regulating epithelial to mesenchymal transition in prostate cancer progression. Materials and Methods: The relative invasion index of prostate cancer cells was assessed by MTT based in vitro invasion assay. Immunoprecipitation and Western blot were done to determine cadherin-complex formation, and catenin and cadherin protein expression. Results: Restoration of E-cadherin expression in nonE-cadherin expressing prostate cancer cells decreased invasive potential. However, in vitro invasive potential was tightly regulated by the interaction of cadherin proteins with the catenin complex. E and N-cadherin, cadherin-11, and the catenin proteins alpha, beta, gamma and p120 are important for the downstream signaling associated with epithelial to mesenchymal transition in tumor cells. Conclusions: Restoration of epithelial specific proteins, such as E-cadherin, in tumor cells can inhibit invasion. However, invasion is a complex process regulated not only by E and N-cadherin but also by catenin-complex proteins. The complex signaling process associated with tumor invasion warrants further investigation since crosstalk between overlapping signaling pathways is involved in regulating prostate cancer invasion, metastasis and progression.