Official websites use. Share sensitive information only on official, secure websites. Address all correspondence and requests for reprints to: Gail S. Prins, Ph. E-mail: gprins uic. Normal human prostate progenitor cells are estrogen targets and estradiol, in an androgen-supported milieu, is capable of transformation and malignant progression of human prostate epithelium. The present study sought to determine whether estrogens with testosterone support are sufficient to transform the normal human prostate epithelium and promote progression to invasive adenocarcinoma using a novel chimeric prostate model.
Recombinants of human prostate progenitor cells with rat urogenital sinus mesenchyme formed chimeric prostate tissue in vivo under the renal capsule of nude mice. These findings provide the first direct evidence that human prostate progenitor cells are estrogen targets and that estradiol in an androgen-supported milieu is a carcinogen for human prostate epithelium. Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer deaths in North American men.
Increasing evidence indicates that in addition to androgens, estrogens play key roles in prostate carcinogenesis and progression; however, the mechanisms are not fully understood 1 β 5. Progress toward understanding the role of sex steroids in the etiology of human prostate cancer has been hindered by the lack of a suitable laboratory research model 6. The only nonhuman mammals known to develop prostate cancer naturally are primates and dogs 7 ; however, both models are expensive and limited by long tumor latencies.
Experimental rodent models have been developed and used extensively to elucidate the mechanisms of prostate carcinogenesis and include transgenic mouse 8 , 9 and rat prostate cancers 10 , spontaneous and chemically inducible Lobund-Wistar rat prostate cancer 11 , 12 , and hormone-inducible Dunning 13 and Noble rat prostate cancers These models, however, are limited by their nonhuman origin, which restricts their direct application to humans.
Prostate cancer models of human origin consist of primary cell or tissue slice cultures 15 , multiple cancer cell lines used in vitro and in vivo as grafts 16 , 17 , as well as cancer tissue xenografts However, these cells and tissues are derived from established prostate cancers that hamper their use in the investigation of initiating events and early transformation. To investigate these early steps in prostate carcinogenesis from normal cells to transformed epithelium, a model using normal human prostate cells is required.
