17-Beta-estradiol induces neoplastic transformation in prostatic epithelial cells
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AbstractAlthough estrogens have been long implicated in the prostate carcinogenesis. direct evidence showing their carcinogenicity on prostatic epithelial cells has not yet been clearly demonstrated. In this study, we treated an immortalized, non-transformed and androgen-responsive rat prostatic epithelial cell line NRP-152 with 17 beta-estradiol (E-2) at concentrations 1-3 mu M for period 2-6 weeks. After in vitro treatment, we evaluated the anchorage-independent growth of E-2-treated NRP-152 cells by soft agar assay and isolated the colonies formed by the transformed E-2-NRP-152 cells in soft agar for further growth phenotype characterization. Our results showed that the isolated E-2-NRP-152 clones displayed neoplastic transformation phenotype, as demonstrated by their capacity of forming colonies in soft agar and tumors in immunodeficient nude mice, while losing their spheroid formation capacity in Matrigel 3D-culture. Western blot and RT-PCR analyses showed that the transformed E-2-NRP-152 cells expressed increased levels of ER alpha and several putative prostate cancer stem cell markers (integrins alpha 2 beta 1, CD44, CD133, ABCG2 and CXCR4) but decreased levels of ER beta and AR. Comet assay revealed that E-2-treatment also induced formation of comet cells, indicating that E-2 caused DNA damage to the NRP-152 cells. Our present findings demonstrated that in vitro E-2 exposure could neoplastically transform the rat prostatic epithelial cells, indicating that E-2 is carcinogenic to the prostatic epithelial cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
All Author(s) ListYu S, Zhang Y, Yuen MT, Zou C, Danielpour D, Chan FL
Journal nameCancer Letters
Year2011
Month5
Day1
Volume Number304
Issue Number1
PublisherELSEVIER IRELAND LTD
Pages8 - 20
ISSN0304-3835
eISSN1872-7980
LanguagesEnglish-United Kingdom
KeywordsEstrogen carcinogenicity; Immortalization; Prostate cancer; Prostatic epithelial cell; Transformation
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2020-15-01 at 00:59