Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 12 April 2011
Vol. 4, Issue 168, p. ra22
[DOI: 10.1126/scisignal.2001551]

RESEARCH ARTICLES

Editor's Summary

Pro- and Antitumorigenic Ligands for Estrogen Receptor
Prostate cancer is a substantial cause of mortality among aging men. Growth of prostate tumors may initially be hormone-dependent and can thus be slowed by androgen ablation therapy; however, these cancers frequently become androgen-independent. Antiestrogens, such as ICI 182,780 (ICI), can block the development and progression of androgen-independent prostate cancers, whereas estrogens can promote growth of these cancers. Nakajima et al. investigated the mechanisms by which estrogens and antiestrogens exert their opposing effects on prostate tumor growth. They found that estrogen receptor β (ERβ) enhanced KLF5-mediated transcription of FOXO1, which encodes a protein that can promote cell death in prostate cancer cells. In contrast, estrogen elicited the association of an ubiquitin ligase with the KLF5-ERβ complex and promoted proteasomal degradation of KLF5. In mice injected with prostate cancer cells, ICI treatment decreased tumor size, whereas estrogen treatment promoted tumor growth. The presence of both ERβ and KLF5 in individuals with prostate tumors correlated with longer survival and histological profiles associated with less aggressive tumors. The accompanying Perspective by Leung and Ho discusses the biological and clinical implications of this research, including the intriguing possibility that estrogens may not be necessary for transcriptional activity of ERβ and thus may not be the primary ligand for ERβ in the prostate.

Citation: Y. Nakajima, K. Akaogi, T. Suzuki, A. Osakabe, C. Yamaguchi, N. Sunahara, J. Ishida, K. Kako, S. Ogawa, T. Fujimura, Y. Homma, A. Fukamizu, A. Murayama, K. Kimura, S. Inoue, J. Yanagisawa, Estrogen Regulates Tumor Growth Through a Nonclassical Pathway that Includes the Transcription Factors ERβ and KLF5. Sci. Signal. 4, ra22 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Glucocorticoid Receptor and KLF15 Regulate Gene Expression Dynamics and Integrate Signals through Feed-Forward Circuitry.
S. K. Sasse, C. M. Mailloux, A. J. Barczak, Q. Wang, M. O. Altonsy, M. K. Jain, S. M. Haldar, and A. N. Gerber (2013)
Mol. Cell. Biol. 33, 2104-2115
   Abstract »    Full Text »    PDF »
FOXO1/3 Depletion in Granulosa Cells Alters Follicle Growth, Death and Regulation of Pituitary FSH.
Z. Liu, D. H. Castrillon, W. Zhou, and J. S. Richards (2013)
Mol. Endocrinol. 27, 238-252
   Abstract »    Full Text »    PDF »
Kruppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens.
K. Takagi, Y. Miki, Y. Onodera, Y. Nakamura, T. Ishida, M. Watanabe, S. Inoue, H. Sasano, and T. Suzuki (2012)
Endocr. Relat. Cancer 19, 741-750
   Abstract »    Full Text »    PDF »
Kruppel-like factor 15 regulates skeletal muscle lipid flux and exercise adaptation.
S. M. Haldar, D. Jeyaraj, P. Anand, H. Zhu, Y. Lu, D. A. Prosdocimo, B. Eapen, D. Kawanami, M. Okutsu, L. Brotto, et al. (2012)
PNAS 109, 6739-6744
   Abstract »    Full Text »    PDF »
Kruppel-like factor 5 (KLF5) is critical for conferring uterine receptivity to implantation.
X. Sun, L. Zhang, H. Xie, H. Wan, B. Magella, J. A. Whitsett, and S. K. Dey (2012)
PNAS 109, 1145-1150
   Abstract »    Full Text »    PDF »
Estrogen Receptor {beta}: Switching to a New Partner and Escaping from Estrogen.
Y.-K. Leung and S.-M. Ho (2011)
Science Signaling 4, pe19
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882