title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmacy, Iwate Medical University.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Soichiro
authors.initials: S
authors.lastname: Kimura
authors.forename: Katsuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbe
authors.forename: Hideo
authors.initials: H
authors.lastname: Ueda
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kudo
mesh_terms: D001940:Breast; D002364:Caseins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D010766:Phosphorylation; D011388:Prolactin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D002364:Caseins; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D012701:Serotonin; D011388:Prolactin; C507924:JAK2 protein, human; D053614:Janus Kinase 2