scholarly journals Skp2B Stimulates Mammary Gland Development by Inhibiting REA, the Repressor of the Estrogen Receptor

2007 ◽  
Vol 27 (21) ◽  
pp. 7615-7622 ◽  
Author(s):  
Karina Umanskaya ◽  
Susanne Radke ◽  
Harish Chander ◽  
Rosie Monardo ◽  
Xinsong Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mammary Gland Development ◽  
Mammary Glands ◽  
Estrogen Receptor Activity ◽  
Development And Differentiation ◽  
F Box Protein ◽  
Gland Development ◽  
Lobuloalveolar Development ◽  
Two Hybrid

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.

scholarly journals Abnormal Mammary Gland Development and Growth Retardation in Female Mice and MCF7 Breast Cancer Cells Lacking Androgen Receptor

2003 ◽  
Vol 198 (12) ◽  
pp. 1899-1908 ◽  
Author(s):  
Shuyuan Yeh ◽  
Yueh-Chiang Hu ◽  
Peng-Hui Wang ◽  
Chao Xie ◽  
Qingquan Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Androgen Receptor ◽  
Growth Factor ◽  
Growth Retardation ◽  
Breast Cancer Cells ◽  
Mammary Gland Development ◽  
Mammary Glands ◽  
Factor I ◽  
Gland Development

Phenotype analysis of female mice lacking androgen receptor (AR) deficient (AR−/−) indicates that the development of mammary glands is retarded with reduced ductal branching in the prepubertal stages, and fewer Cap cells in the terminal end buds, as well as decreased lobuloalveolar development in adult females, and fewer milk-producing alveoli in the lactating glands. The defective development of AR−/− mammary glands involves the defects of insulin-like growth factor I–insulin-like growth factor I receptor and mitogen-activated protein kinase (MAPK) signals as well as estrogen receptor (ER) activity. Similar growth retardation and defects in growth factor–mediated Ras/Raf/MAPK cascade and ER signaling are also found in AR−/− MCF7 breast cancer cells. The restoration assays show that AR NH2-terminal/DNA-binding domain, but not the ligand-binding domain, is essential for normal MAPK function in MCF7 cells, and an AR mutant (R608K), found in male breast cancer, is associated with the excessive activation of MAPK. Together, our data provide the first in vivo evidence showing that AR-mediated MAPK and ER activation may play important roles for mammary gland development and MCF7 breast cancer cell proliferation.

scholarly journals Histone Demethylase JMJD2B Functions as a Co-Factor of Estrogen Receptor in Breast Cancer Proliferation and Mammary Gland Development

PLoS ONE ◽  
2011 ◽  
Vol 6 (3) ◽  
pp. e17830 ◽  
Author(s):  
Masahito Kawazu ◽  
Kayoko Saso ◽  
Kit I. Tong ◽  
Tracy McQuire ◽  
Kouichiro Goto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Histone Demethylase ◽  
Cancer Proliferation ◽  
Gland Development

scholarly journals Role of F-Box Protein βTrcp1 in Mammary Gland Development and Tumorigenesis

2004 ◽  
Vol 24 (18) ◽  
pp. 8184-8194 ◽  
Author(s):  
Yasusei Kudo ◽  
Daniele Guardavaccaro ◽  
Patricia G. Santamaria ◽  
Ryo Koyama-Nasu ◽  
Esther Latres ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Transgenic Mice ◽  
Mammary Gland Development ◽  
Mammary Glands ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Ductal Branching ◽  
F Box Protein ◽  
Gland Development

ABSTRACT The F-box protein βTrcp1 controls the stability of several crucial regulators of proliferation and apoptosis, including certain inhibitors of the NF-κB family of transcription factors. Here we show that mammary glands of βTrcp1−/− female mice display a hypoplastic phenotype, whereas no effects on cell proliferation are observed in other somatic cells. To investigate further the role of βTrcp1 in mammary gland development, we generated transgenic mice expressing human βTrcp1 targeted to epithelial cells under the control of the mouse mammary tumor virus (MMTV) long terminal repeat promoter. Compared to controls, MMTV βTrcp1 mammary glands display an increase in lateral ductal branching and extensive arrays of alveolus-like protuberances. The mammary epithelia of MMTV βTrcp1 mice proliferate more and show increased NF-κB DNA binding activity and higher levels of nuclear NF-κB p65/RelA. In addition, 38% of transgenic mice develop tumors, including mammary, ovarian, and uterine carcinomas. The targeting of βTrcp1 to lymphoid organs produces no effects on these tissues. In summary, our results support the notion that βTrcp1 positively controls the proliferation of breast epithelium and indicate that alteration of βTrcp1 function and expression may contribute to malignant behavior of breast tumors, at least in part through NF-κB transactivation.

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