scholarly journals Regulatory function of whey acidic protein in the proliferation of mouse mammary epithelial cells in vivo and in vitro

2004 ◽  
Vol 274 (1) ◽  
pp. 31-44 ◽  
Author(s):  
Naoko Nukumi ◽  
Kayoko Ikeda ◽  
Megumi Osawa ◽  
Tokuko Iwamori ◽  
Kunihiko Naito ◽  
...  
2008 ◽  
Vol 22 (12) ◽  
pp. 2677-2688 ◽  
Author(s):  
Paul G. Tiffen ◽  
Nader Omidvar ◽  
Nuria Marquez-Almuina ◽  
Dawn Croston ◽  
Christine J. Watson ◽  
...  

Abstract Recent studies in breast cancer cell lines have shown that oncostatin M (OSM) not only inhibits proliferation but also promotes cell detachment and enhances cell motility. In this study, we have looked at the role of OSM signaling in nontransformed mouse mammary epithelial cells in vitro using the KIM-2 mammary epithelial cell line and in vivo using OSM receptor (OSMR)-deficient mice. OSM and its receptor were up-regulated approximately 2 d after the onset of postlactational mammary regression, in response to leukemia inhibitory factor (LIF)-induced signal transducer and activator of transcription-3 (STAT3). This resulted in sustained STAT3 activity, increased epithelial apoptosis, and enhanced clearance of epithelial structures during the remodeling phase of mammary involution. Concurrently, OSM signaling precipitated the dephosphorylation of STAT5 and repressed expression of the milk protein genes β-casein and whey acidic protein (WAP). Similarly, during pregnancy, OSM signaling suppressed β-casein and WAP gene expression. In vitro, OSM but not LIF persistently down-regulated phosphorylated (p)-STAT5, even in the continued presence of prolactin. OSM also promoted the expression of metalloproteinases MMP3, MMP12, and MMP14, which, in vitro, were responsible for OSM-specific apoptosis. Thus, the sequential activation of IL-6-related cytokines during mammary involution culminates in an OSM-dependent repression of epithelial-specific gene expression and the potentiation of epithelial cell extinction mediated, at least in part, by the reciprocal regulation of p-STAT5 and p-STAT3.


2007 ◽  
Vol 213 (3) ◽  
pp. 793-800 ◽  
Author(s):  
Naoko Nukumi ◽  
Tokuko Iwamori ◽  
Kiyoshi Kano ◽  
Kunihiko Naito ◽  
Hideaki Tojo

2020 ◽  
Vol 64 (24) ◽  
pp. 2000853
Author(s):  
Norihiro Suzuki ◽  
Yusaku Tsugami ◽  
Haruka Wakasa ◽  
Takahiro Suzuki ◽  
Takanori Nishimura ◽  
...  

2005 ◽  
Vol 1726 (1) ◽  
pp. 48-56 ◽  
Author(s):  
Jorge R. Toledo ◽  
Oliberto Sánchez ◽  
Raquel Montesino Seguí ◽  
Yaiza Fernández García ◽  
María P. Rodríguez ◽  
...  

1995 ◽  
Vol 98 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Jason Yang ◽  
Tetsuya Tsukamoto ◽  
Nikolay Popnikolov ◽  
Raphael C. Guzman ◽  
Xiaoyan Chen ◽  
...  

1989 ◽  
Vol 182 (2) ◽  
pp. 653-658 ◽  
Author(s):  
Stephen P. Ethier ◽  
Rochelle M. Van De Velde ◽  
Kimberly C. Cundiff

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