Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor.
Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor.
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Skp2B 通过抑制 REA（雌激素受体的抑制因子）来刺激乳腺发育。
DOI：
10.1128/mcb.01239-07
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发表时间：
2007
影响因子：
5.3
通讯作者：
Germain,Doris
中科院分区：
文献类型：
--
作者：
Umanskaya,Karina;Radke,Susanne;Chander,Harish;Monardo,Rosie;Xu,Xinsong;Pan,Zhen-Qiang;O'Connell,MatthewJ;Germain,Doris
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.
