Prostate development and carcinogenesis

The process involved in the development and carcinogenesis of the prostate gland is complex. During early prostate development, the androgenic hormone from embryonic testicles is required for ductal formation, growth, and branching morphogenesis of the prostate gland. From this early stage, interactions between the epithelium and mesenchyme become firmly established through paracrine influence (i.e., growth factors) from mesenchyme (stroma), in response to testosterone, acting on epithelium to stimulate its proliferation, morphogenetic differentiation, and function. In return, the epithelium also exerts its paracrine effects on mesenchyme by regulating the differentiation and specific organizational pattern of its stromal smooth muscle. In a normal adult prostate, the maintenance of normal glandular structure and function is dependent not only on the constant presence of testosterone, but also on a normal intact and stable stroma. This chapter will concentrate first on factors involved in the normal development of the prostate gland and then on the aberrant changes in the homeostatic balance arising either from within (i.e., mutations) or outside (i.e., changes in hormonal balance) that result in derangements of the prostate gland. Finally, environmental and genetic factors that lead to prostate carcinogenesis including activation of oncogenes and mutations of tumor suppressor genes are also discussed.