Endocrine Disruption and Human Prostate Cancer; Final rept. 1 Mar 2007-28 Feb 2008

摘要

Endocrine disrupting chemicals (EDCs) are present in our everyday life and many of them act to oppose androgens including the fungicide, Vinclozolin. Most of the studies on EDCs are conducted in rodents and have limited utility when extrapolating the findings to humans. In order to test the concept that Vinclozolin alters human prostate development and induces disease, we used our model system to study human prostate development and maturation over 8-12 weeks, comparable to the process that takes decades in men. Briefly we use rodent stroma to create a niche in which human stem cells are directed to become human prostatic epithelia. Task 1 sought to test if the rodent stromal niche (obtained after exposure to Vinclozolin) was altered so that differentiation and development to normal human prostate tissue was aberrant leading to a disease phenotype. Surprisingly, our results showed development of the prostatic phenotype was completely blocked and was not predicted. These novel findings are fundamental to understanding how normal prostatic differentiation proceeds and our publications show the essential role of stroma is perturbed by Vinclozolin, define the prostatic phenotype induced by Vinclozolin and demonstrate the involvement of NFkB signalling pathways.