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Molecular and Cellular Biology, November 2007, p. 7615-7622, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.01239-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Skp2B Stimulates Mammary Gland Development by Inhibiting REA, the Repressor of the Estrogen Receptor{triangledown}

Karina Umanskaya,1 Susanne Radke,1 Harish Chander,1 Rosie Monardo,1 Xinsong Xu,2 Zhen-Qiang Pan,2 Matthew J. O'Connell,2 and Doris Germain1*

Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1178, New York, New York 10029,1 Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York2

Received 11 July 2007/ Accepted 21 August 2007

Skp2B, an F-box protein of unknown function, is frequently overexpressed in breast cancer. In order to determine the function of Skp2B and whether it has a role in breast cancer, we performed a two-hybrid screen and established transgenic mice expressing Skp2B in the mammary glands. We found that Skp2B interacts with the repressor of estrogen receptor activity (REA) and that overexpression of Skp2B leads to a reduction in REA levels. In the mammary glands of MMTV-Skp2B mice, REA levels are also low. Our results show that in virgin transgenic females, Skp2B induces lobuloalveolar development and differentiation of the mammary glands normally observed during pregnancy. As this phenotype is identical to what was observed for REA heterozygote mice, our observations suggest that the Skp2B-REA interaction is physiologically relevant. However, in contrast to REA+/– mice, MMTV-Skp2B mice develop mammary tumors, suggesting that Skp2B affects additional proteins. These results indicate that the observed expression of Skp2B in breast cancer does contribute to tumorigenesis at least in part by modulating the activity of the estrogen receptor.

* Corresponding author. Mailing address: Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1178, New York, NY 10029. Phone: (212) 241-9541. Fax: (212) 996-5787. E-mail: doris.germain{at}mssm.edu

{triangledown} Published ahead of print on 4 September 2007.

Molecular and Cellular Biology, November 2007, p. 7615-7622, Vol. 27, No. 21
0270-7306/07/$08.00+0     doi:10.1128/MCB.01239-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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