scholarly journals Inhibitory Function of Whey Acidic Protein in the Cell-Cycle Progression of Mouse Mammary Epithelial Cells (EpH4 / K6 Cells)

2004 ◽  
Vol 50 (1) ◽  
pp. 87-96 ◽  
Author(s):  
Kayoko IKEDA ◽  
Naoko NUKUMI ◽  
Tokuko IWAMORI ◽  
Megumi OSAWA ◽  
Kunihiko NAITO ◽  
...  
2005 ◽  
Vol 280 (43) ◽  
pp. 36301-36309 ◽  
Author(s):  
Sandra L. Grimm ◽  
Alejandro Contreras ◽  
Mary-Helen Barcellos-Hoff ◽  
Jeffrey M. Rosen

In contrast to hormone-dependent breast cancer, steroid hormone-induced proliferation in the normal mammary gland does not occur in the steroid-receptor positive cells but rather in adjacent cells via paracrine signaling involving several local growth factors. To help elucidate the mechanisms involved in the block in proliferation in hormone-receptor positive cells, we have utilized a CCAAT/enhancer binding protein (C/EBPβ)-null mouse model. Loss of this transcription factor results in increased steroid and prolactin receptor expression concomitant with a 10-fold decrease in proliferation in response to pregnancy hormones. To determine the basis for this decrease, several markers of cell cycle progression were analyzed in wild type and C/EBPβ-null mammary epithelial cells (MECs). These studies indicated that cell cycle progression in C/EBPβ-null MECs is blocked at the G1/S transition. C/EBPβ-null mammary glands display substantially increased levels of the activated form of transforming growth factor β, a potent inhibitor of epithelial cell proliferation, as well as increased downstream Smad2 expression and signaling. While cyclin D1 levels were equivalent, cyclin E expression was markedly reduced in C/EBPβ-null as compared with wildtype MECs. In addition, increased p27 stability and retention in the nucleus and decreased levels of the cdc25a phosphatase contributed to a significant loss of cdk2 kinase activity. Collectively, these changes prevent C/EBPβ-null mammary epithelial cells from responding to hormone-induced proliferative signals.


2004 ◽  
Vol 274 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Naoko Nukumi ◽  
Kayoko Ikeda ◽  
Megumi Osawa ◽  
Tokuko Iwamori ◽  
Kunihiko Naito ◽  
...  

genesis ◽  
2005 ◽  
Vol 43 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Aleata A. Triplett ◽  
Kazuhito Sakamoto ◽  
Laurice A. Matulka ◽  
Liya Shen ◽  
Gilbert H Smith ◽  
...  

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