Serotonin Regulates β-Casein Expression via 5-HT₇ Receptors in Human Mammary Epithelial MCF-12A Cells

• Chiba Takeshi

  Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University

• Kimura Soichiro

  Department of Hospital Pharmacy, Faculty 
of Pharmaceutical Sciences, Josai University

• Takahashi Katsuo

  Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University

• Morimoto Yasunori

  Department of Hospital Pharmacy, Faculty 
of Pharmaceutical Sciences, Josai University

• Maeda Tomoji

  Department 
of Neuroscience, School of Pharmacy, Iwate Medical University

• Sanbe Atsushi

  Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University

• Ueda Hideo

  Department of Hospital Pharmacy, Faculty 
of Pharmaceutical Sciences, Josai University

• Kudo Kenzo

  Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University

書誌事項

タイトル別名

• Serotonin Regulates β-Casein Expression <i>via</i> 5-HT₇ Receptors in Human Mammary Epithelial MCF-12A Cells

抄録

We previously reported that serotonin (5-hydroxytryptamine; 5-HT) suppresses β-casein expression, a differentiation marker in mammary epithelial cells, via inhibition of the signal transducer and activator of transcription 5 (STAT5) phosphorylation in the human mammary epithelial cell line, MCF-12A. In this study, we investigated the expression pattern of the different 5-HT receptor subtypes in MCF-12A cells, and identified the receptors involved in 5-HT-mediated suppression of β-casein protein expression. β-Casein mRNA expression was inhibited by 30 µM 5-HT in a time-dependent manner. Treatment with 30 µM 5-HT for 72 h decreased β-casein protein levels and STAT5 phosphorylation (pSTAT5). The cells expressed four 5-HT receptors subtypes (5-HTR_{1D, 2B, 3A, and 7}) at the mRNA and protein level, and their expression was elevated by prolactin (PRL) treatment. Additionally, the mRNA levels of 5-HTR_1D and 5-HTR₇ were significantly higher than the other 5-HT receptors in the cells. Tryptophan hydroxylase 1 mRNA was detectable in the cells in the absence of PRL, and PRL treatment significantly increased its expression. β-Casein and pSTAT5/STAT5 levels in the cells co-treated with 5-HT and a selective 5-HTR_1D inhibitor, BRL15572, were equal to those observed in cells treated with 5-HT alone. However, in the cells co-treated with 5-HT and a selective 5-HTR₇ inhibitor, SB269970, β-casein and pSTAT5/STAT5 levels increased in a SB269970 concentration-dependent manner. In conclusion, we showed that 5-HT regulates β-casein expression via 5-HTR₇ in MCF-12A human mammary epithelial cells.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (3), 448-453, 2015

  公益社団法人 日本薬学会

キーワード

• serotonin
• β-casein
• 5-hydroxytryptamine (5-HT)₇ receptor
• human mammary gland
• milk protein

詳細情報

• CRID: 1390282679608056064
• NII論文ID: 130004872286
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00723
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026193309
• PubMed: 25757927
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026193309
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/3/38_b14-00723/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015360257
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可