Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor.

Abstract:

: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.

journal_name

Mol Cell Biol

authors

Umanskaya K,Radke S,Chander H,Monardo R,Xu X,Pan ZQ,O'Connell MJ,Germain D

doi

10.1128/MCB.01239-07

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

7615-22

issue

21

eissn

0270-7306

issn

1098-5549

pii

MCB.01239-07

journal_volume

27

pub_type

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