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

• Published in: Biological & pharmaceutical bulletin Vol. 37; no. 8; pp. 1336 - 1340
• Main Authors: Chiba, Takeshi, Kimura, Soichiro, Takahashi, Katsuo, Morimoto, Yasunori, Sanbe, Atsushi, Ueda, Hideo, Kudo, Kenzo
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.08.2014
• Subjects: Breast; Caseins - genetics; Caseins - metabolism; Cell Line; Cell Survival - drug effects; Epithelial Cells - drug effects; Epithelial Cells - metabolism; human mammary gland; Humans; Janus Kinase 2 - metabolism; MCF-12A; milk protein; Phosphorylation; Prolactin - pharmacology; Receptors, Prolactin - genetics; RNA, Messenger - metabolism; serotonin; Serotonin - pharmacology; STAT5 Transcription Factor - antagonists & inhibitors; STAT5 Transcription Factor - metabolism; β-casein
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00273

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.