Serotonin Suppresses β-Casein Expression via Inhibition of the Signal Transducer and Activator of Transcription 5 (STAT5) Protein Phosphorylation in Human Mammary Epithelial Cells MCF-12A
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概要
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Serotonin (5-hydroxytryptamine; 5-HT) has an important physiological role in controlling lactation, namely, milk volume homeostasis, within mammary glands. The objectives of this study were to evaluate whether exogenous 5-HT can suppress β-casein expression, a differentiation marker, produced in human mammary epithelial cells, and to determine whether 5-HT can attenuate β-casein signaling via the prolactin (PRL) receptor (PRLr) and Janus kinase 2/signal transducer and activator of transcription 5 (STAT5) pathway. PRL treatment increased the mRNA level of β-casein in the MCF-12A human mammary epithelial cell line, and the highest level occurred at days 7 and 14 of culture. In contrast, PRLr expression was not affected significantly by PRL treatment. PRL treatment in MCF-12A cells increased levels of β-casein and phosphorylated STAT5 (pSTAT5) proteins in a concentration-dependent manner, with a slight increase of STAT5 protein. β-Casein expression was inhibited by 0.1 mM 5-HT in a time-dependent manner. Additionally, treatment with 0.1 mM 5-HT for 72 h decreased protein levels of β-casein and pSTAT5, with a slight decrease in STAT5 levels. These results suggest that exogenous 5-HT can inhibit STAT5 phosphorylation, resulting in a decrease in β-Casein expression. In conclusion, we showed that exogenous 5-HT decreased β-casein expression in MCF-12A human mammary epithelial cells, and that 5-HT was responsible for inhibiting phosphorylation of STAT5, resulting in a decline in lactational function.
- 公益社団法人 日本薬学会の論文
著者
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Kimura Soichiro
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Josai University
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Morimoto Yasunori
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Josai University
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Chiba Takeshi
Department Of Functional Molecular Chemistry Kobe Pharmaceutical University
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Sanbe Atsushi
Department Of Pharmacology National Research Institute For Child Health And Development
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Takahashi Katsuo
Department Of Pharmacy Iwate Medical University Hospital
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Ueda Hideo
Department Of Computer Science And Electronics Kyushu Institute Of Technology
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Kudo Kenzo
Department Of Pharmacology School Of Medicine Iwate Medical University
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Sanbe Atsushi
Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University
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