A novel cell-cell recombination model was established to test the reciprocal mesenchymal (fibroblast)-epithelial interaction in the prostate gland. Both growth factors and ECM pathways were found to be actively engaged during cellular communications. The application of this cell-cell recombination concept to prostate cancer established a new human prostate cancer animal model in which the tumours actively secrete prostate specific antigen, a known human prostate cancer marker. This review explores the significance of mesenchymal-epithelial interaction in determining prostate hormonal responsiveness and prostate cell transformation and speculates on the potential roles of mesenchymal-epithelial interaction in prostate cancer growth and progression.