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.


Sci. STKE, 25 June 2002
Vol. 2002, Issue 138, p. tw224
[DOI: 10.1126/stke.2002.138.tw224]

EDITORS' CHOICE

Cell Cycle Mechanism for Estrogen-Induced Proliferation

Uranon et al. present evidence for a mechanism by which estrogen may promote cell proliferation important in organ development and growth of some breast cancers. Active estrogen receptor alpha causes increased transcription of the gene encoding Efp, a protein required for estrogen-induced cell proliferation. Inhibition of Efp expression with antisense oligonucleotides inhibited growth of MCF7 breast cancer cells transplanted in mice. In a yeast two-hybrid screen, the authors detected interaction of Efp with the 14-3-3{sigma} protein, which inhibits cell-cycle progression, probably by interacting with the cyclin-dependent kinases Cdk2 and Cdc2. In transiently transfected cells, interaction of Efp and 14-3-3{sigma} was detected by immunoprecipitation. Expression of Efp reduced the amount of 14-3-3{sigma} present in cells, and pulse chase analysis showed that degradation of 14-3-3{sigma} was enhanced. The authors propose that Efp may function as an E3 ubiquitin ligase for 14-3-3{sigma}, because Efp contains characteristic RING finger domains. Consistent with this interpretation, transfection of cells with Efp and the ubiquitin-conjugating enzyme UbcH8 increased ubiquitination of 14-3-3{sigma}. In mouse embryo fibroblasts lacking Efp, proliferation was inhibited, and the abundance of 14-3-3{sigma} was greater than that in wild-type cells. Proliferation could be restored by treatment of the cells with antisense oligonucleotides to 14-3-3{sigma}. Together, the results indicate that Efp may promote cell proliferation by enhancing degradation of 14-3-3{sigma}. Blocking such effects of Efp might be advantageous in strategies to halt proliferation of breast tumor cells.

T. Urano, T. Saito, T. Tsukui, M. Fujita, T. Hosoi, M. Muramatsu, Y. Ouchi, S. Inoue, Efp targets 14-3-3{sigma} for proteolysis and promotes breast tumour growth. Nature 417, 871-875 (2002). [Online Journal]

Citation: Mechanism for Estrogen-Induced Proliferation. Sci. STKE 2002, tw224 (2002).


To Advertise     Find Products


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