title: A human fetal prostate xenograft model of developmental estrogenization.
abstract: Prostate cancer is a common disease in older men. Rodent models have demonstrated that an early and later-life exposure to estrogen can lead to cancerous lesions and implicated hormonal dysregulation as an avenue for developing future prostate neoplasia. This study utilizes a human fetal prostate xenograft model to study the role of estrogen in the progression of human disease. Histopathological lesions were assessed in 7-, 30-, 90-, 200-, and 400-day human prostate xenografts. Gene expression for cell cycle, tumor suppressors, and apoptosis-related genes (ie, CDKN1A, CASP9, ESR2, PTEN, and TP53) was performed for 200-day estrogen-treated xenografts. Glandular hyperplasia was observed in xenografts given both an initial and secondary exposure to estradiol in both 200- and 400-day xenografts. Persistent estrogenic effects were verified using immunohistochemical markers for cytokeratin 10, p63, and estrogen receptor α. This model provides data on the histopathological state of the human prostate following estrogenic treatment, which can be utilized in understanding the complicated pathology associated with prostatic disease and early and later-life estrogenic exposures.
authors: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
authors: Camelia M
authors: CM
authors: Saffarini
authors: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
authors: Elizabeth V
authors: EV
authors: McDonnell-Clark
authors: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA Department of Pathology and Laboratory Medicine, Rhode Island Hospital, Providence, RI, USA.
authors: Ali
authors: A
authors: Amin
authors: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA kim_boekelheide@brown.edu.
authors: Kim
authors: K
authors: Boekelheide
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004958:Estradiol / Q000009:adverse effects / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D064593:Heterografts / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000196:embryology / Q000378:metabolism / Q000637:transplantation*; D011470:Prostatic Hyperplasia / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D011923:Rats, Nude; D013739:Testosterone / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D013739:Testosterone; D004958:Estradiol
keywords: animal models; developmental pathology; environmental toxicology; prostate; reproductive system
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