title: Serotonin regulates β-casein expression via 5-HT7 receptors in human mammary epithelial MCF-12A cells.
abstract: 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-HTR1D, 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-HTR1D 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-HTR1D 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.
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: Tomoji
authors.initials: T
authors.lastname: Maeda
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 / Q000378:metabolism*; D002364:Caseins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D002364:Caseins; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D050799:STAT5 Transcription Factor; C104425:serotonin 7 receptor; D012701:Serotonin; D011388:Prolactin; D014365:Tryptophan Hydroxylase; D053614:Janus Kinase 2