TGF-β inhibits prolactin-induced expression of β-casein by a Smad3-dependent mechanism

doi:10.1002/jcb.21734

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/3528

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/3528

Title:	TGF-β inhibits prolactin-induced expression of β-casein by a Smad3-dependent mechanism
Authors:	Wen-Jun Wu;Chin-Feng Lee;Chung-Han Hsin;Jyun-Yi Du;Tsai-Ching Hsu;Ting-Hui Lin;Tsung-You Yao;Cheng-Hsieh Huang;Yi-Ju Lee
Contributors:	中山醫學大學：醫學系
Keywords:	mammary gland;prolactin;β-casein;TGF-β;Smad3
Date:	2008
Issue Date:	2011-03-10T08:49:03Z (UTC)
ISSN:	0006-291X
Abstract:	Transforming growth factor-β (TGF-β) is a multifunctional growth factor, affecting cell proliferation, apoptosis, and extracellular matrix homeostasis. It also plays critical roles in mammary gland development, one of which involves inhibition of the expression of milk proteins, such as β-casein, during pregnancy. Here we further explore the underlying signaling mechanism for it. Our results show that TGF-β suppresses prolactin-induced expression of β-casein mRNA and protein in primary mouse mammary epithelial cells, but its effect on protein expression is more evident. We also find out that this inhibition is not due to the effect of TGF-β on cell apoptosis. Furthermore, inhibition of TGF-β type I receptor kinase activity by a pharmacological inhibitor SB431542 or overexpression of dominant negative Smad3 substantially restores β-casein expression. By contrast, inhibition of p38 and Erk that are known to be activated by TGF-β does not alleviate the inhibitory effect of TGF-β. These results are consistent with our other observation that Smad but not MAPK pathway is activated by TGF-β in mammary epithelial cells. Lastly, we show that prolactin-induced tyrosine phosphorylation of Jak2 and Stat5 as well as serine/threonine phosphorylation of p70S6K and S6 ribosomal protein are downregulated by TGF-β, although the former event requires considerably long exposure to TGF-β. We speculate that these events might be involved in repressing transcription and translation of β-casein gene, respectively. Taken together, our results demonstrate that TGF-β abrogates prolactin-stimulated β-casein gene expression in mammary epithelial cells through, at least in part, a Smad3-dependent mechanism
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3528 http://dx.doi.org/10.1002/jcb.21734
Relation:	Journal of Cellular Biochemistry,Volume 104, Issue 5, pages 1647–1659, 1 August 2008
Appears in Collections:	[醫學系] 期刊論文

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