NDLI: Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway

Content Provider	PubMed Central
Author	Nakajima, Yuka Asami, Osakabe Waku, Tsuyoshi Suzuki, Takashi Akaogi, Kensuke Fujimura, Tetsuya Homma, Yukio Inoue, Satoshi Yanagisawa, Junn
Copyright Year	2015
Abstract	Estrogens are effective in the treatment of prostate cancer; however, the effects of estrogens on prostate cancer are enigmatic. In this study, we demonstrated that estrogen (17β-estradiol [E2]) has biphasic effects on prostate tumor growth. A lower dose of E2 increased tumor growth in mouse xenograft models using DU145 and PC-3 human prostate cancer cells, whereas a higher dose significantly decreased tumor growth. We found that anchorage-independent apoptosis in these cells was inhibited by E2 treatment. Similarly, in vivo angiogenesis was suppressed by E2. Interestingly, these effects of E2 were abolished by knockdown of either estrogen receptor β (ERβ) or Krüppel-like zinc finger transcription factor 5 (KLF5). Ιn addition, E2 suppressed KLF5-mediated transcription through ERβ, which inhibits proapoptotic FOXO1 and proangiogenic PDGFA expression. Furthermore, we revealed that a nonagonistic ER ligand GS-1405 inhibited FOXO1 and PDGFA expression through the ERβ-KLF5 pathway and regulated prostate tumor growth without ERβ transactivation. Therefore, these results suggest that E2 biphasically modulates prostate tumor formation by regulating KLF5-dependent transcription through ERβ and provide a new strategy for designing ER modulators, which will be able to regulate prostate cancer progression with minimal adverse effects due to ER transactivation.
Related Links	http://dx.doi.org/10.1128/mcb.00625-15
Ending Page	156
Page Count	13
Starting Page	144
File Format	PDF
ISSN	02707306
e-ISSN	10985549
Journal	Molecular and Cellular Biology
Issue Number	1
Volume Number	36
Language	English
Publisher	American Society for Microbiology
Publisher Date	2015-10-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Cell Biology Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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