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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Dual action of high estradiol doses on MNU-induced prostate neoplasms in a rodent model with high serum testosterone: Protective effect and emergence of unstable epithelial microenvironment

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Author(s):
Goncalves, Bianca F. ; de Campos, Silvana G. P. ; Goes, Rejane M. ; Scarano, Wellerson R. ; Taboga, Sebastiao R. ; Vilamaior, Patricia S. L.
Total Authors: 6
Document type: Journal article
Source: PROSTATE; v. 77, n. 9, p. 970-983, JUN 15 2017.
Web of Science Citations: 2
Abstract

BACKGROUNDEstrogens are critical players in prostate growth and disease. Estrogen therapy has been the standard treatment for advanced prostate cancer for several decades; however, it has currently been replaced by alternative anti-androgenic therapies. Additionally, studies of its action on prostate biology, resulting from an association between carcinogens and estrogen, at different stages of life are scarce or inconclusive about its protective and beneficial role on induced-carcinogenesis. Thus, the aim of this study was to determine whether estradiol exerts a protective and/or stimulatory role on N-methyl-N-nitrosurea-induced prostate neoplasms. METHODSWe adopted a rodent model that has been used to study induced-prostate carcinogenesis: the Mongolian gerbil. We investigated the occurrence of neoplasms, karyometric patterns, androgen and estrogen receptors, basal cells, and global methylation status in ventral and dorsolateral prostate tissues. RESULTSHistopathological analysis showed that estrogen was able to slow tumor growth in both lobes after prolonged treatment. However, a true neoplastic regression was observed only in the dorsolateral prostate. In addition to the protective effects against neoplastic progression, estrogen treatment resulted in an epithelium that exhibited features distinctive from a normal prostate, including increased androgen-insensitive basal cells, high androgens and estrogen receptor positivity, and changes in DNA methylation patterns. CONCLUSIONSEstrogen was able to slow tumor growth, but the epithelium exhibited features distinct from a normal prostatic epithelium, and this unstable microenvironment could trigger lesion recurrence over time. (AU)

FAPESP's process: 08/11236-7 - Prostate carcinogenesis chemically induced by N-methyl-N-nitrosourea (MNU) in Mongolian gerbils: association with steroids promoters and high-fat diet
Grantee:Bianca Facchim Gonçalves
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)