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

Mol Cell Biol. 2007 Nov;27(21):7615-22. doi: 10.1128/MCB.01239-07. Epub 2007 Sep 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Cell Differentiation
  • Cysts / pathology
  • Female
  • Humans
  • Hyperplasia
  • Mammary Glands, Animal / growth & development*
  • Mammary Glands, Animal / pathology
  • Mammary Tumor Virus, Mouse
  • Mice
  • Mice, Transgenic
  • Neoplasms / pathology
  • Prohibitins
  • Protein Binding
  • Receptors, Estrogen / antagonists & inhibitors*
  • Receptors, Estrogen / genetics
  • Repressor Proteins / antagonists & inhibitors*
  • S-Phase Kinase-Associated Proteins / metabolism*
  • Sexual Behavior
  • Sexual Maturation
  • Transcription, Genetic
  • Ubiquitin / metabolism


  • PHB2 protein, human
  • Prohibitins
  • Receptors, Estrogen
  • Repressor Proteins
  • S-Phase Kinase-Associated Proteins
  • Ubiquitin