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Official websites use. Share sensitive information only on official, secure websites. Corresponding author: Neil A. Stromal-epithelial interactions mediated by paracrine signaling mechanisms dictate prostate development and progression of prostate cancer. The regulatory role of androgens in both the prostate stromal and epithelial compartments set the prostate apart from many other organs and tissues with regard to gene targeting.
The identification of androgen-dependent prostate epithelial promoters has allowed successful gene targeting to the prostate epithelial compartment. Currently, there are no transgenic mouse models available to specifically alter gene expression within the prostate stromal compartment. As a primary metastatic site for prostate cancer is bone, the functional dissection of the bone stromal compartment is important for understanding stromal-epithelial interactions associated with metastatic tumor growth.
Use of currently available methodologies for the expression or deletion of gene expression in recent research studies has advanced our understanding of the stroma. However, the complexity of stromal heterogeneity within the prostate remains a challenge to obtaining compartment or cell-lineage specific in vivo models necessary for furthering our understanding of prostatic developmental, benign, tumorigenic, and metastatic growth.
The role of mesenchymal tissues in the control of organogenesis has been well established in many organs including the prostate Wolff, ; Cunha, ; Slavkin, ; Cunha et al. The prostate develops from an ambisexual embryonic rudiment, the endodermal urogenital sinus UGS. The prostatic urethra and bulbourethral glands in males, the lower vagina and urethra in females, and bladder in both sexes also develops from the UGS.
Embryonic connective tissue surrounding the UGS, referred to as urogenital mesenchyme UGM , expresses androgen receptors and responds to fetal testicular androgens by promoting epithelial development and differentiation. Embryonic development of the prostatic glandular epithelium proceeds from the outward expansion of cords of urogenital epithelium UGE from the UGS into the UGM resulting in the formation of prostatic buds.