Dataset Information

Genistein Directly Represses the Phosphorylation of STAT5 in Lactating Mammary Epithelial Cells.

ABSTRACT: Genistein is a soy isoflavone and shows various physiological activities, such as affinities for estrogen receptors (ERs) and inhibitory effects on the epidermal growth factor receptor (EGFR) pathway. A previous study reported that genistein downregulates milk production ability in mammary epithelial cells (MECs) while decreasing the phosphorylation of STAT5. The ER and EGFR pathways indirectly regulate STAT5. In this study, the repressing mechanism of genistein against the phosphorylation of STAT5 was investigated using a culture model of mouse MECs with milk production ability. The results revealed that genistein did not influence the behavior of ERα and ERβ, whereas genistein immediately repressed the phosphorylation of ERK1/2. However, the decrease in phosphorylated STAT5 occurred independent of the phosphorylation of EGFR. Genistein repressed new phosphorylation of STAT5 by prolactin without influencing the phosphorylation of JAK2. In conclusion, this study indicates that genistein directly inhibits the phosphorylation of STAT5 in lactating MECs.

SUBMITTER: Tsugami Y

PROVIDER: S-EPMC8427774 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Genistein Directly Represses the Phosphorylation of STAT5 in Lactating Mammary Epithelial Cells.

Tsugami Yusaku Y Wakasa Haruka H Nishimura Takanori T Kobayashi Ken K

ACS omega 20210825 35

Genistein is a soy isoflavone and shows various physiological activities, such as affinities for estrogen receptors (ERs) and inhibitory effects on the epidermal growth factor receptor (EGFR) pathway. A previous study reported that genistein downregulates milk production ability in mammary epithelial cells (MECs) while decreasing the phosphorylation of STAT5. The ER and EGFR pathways indirectly regulate STAT5. In this study, the repressing mechanism of genistein against the phosphorylation of ST ...[more]

PMID: 34514247

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Project description:Maspin (SerpinB5) is a non-inhibitory serpin (serine protease inhibitor) with very diverse biological activities including regulation of cell adhesion, migration, death, control of gene expression and oxidative stress response. Initially described as a tumor and metastasis suppressor, clinical data brought controversies to the field, as some studies reported no correlation between SerpinB5 expression and prognosis value. These data underscore the importance of understanding SerpinB5 function in a normal physiological context and the molecular mechanism involved. Several SerpinB5 phosphoforms have been detected in different cell lines, but the signaling pathways involved and the biological significance of this post-translational modification in vivo remains to be explored. In this study we investigated SerpinB5 expression, subcellular localization and phosphorylation in different stages of the mouse mammary gland development and the signaling pathway involved. Here we show that SerpinB5 is first detected in late pregnancy, reaches its highest levels in lactation and remains at constant levels during post-lactational regression (involution). Using high resolution isoelectric focusing followed but immunoblot, we found at least 8 different phosphoforms of SerpinB5 during lactation, which decreases steadily at the onset of involution. In order to investigate the signaling pathway involved in SerpinB5 phosphorylation, we took advantage of the non-transformed MCF-10A model system, as we have previously observed SerpinB5 phosphorylation in these cells. We detected basal levels of SerpinB5 phosphorylation in serum- and growth factor-starved cells, which is due to amphiregulin autocrine activity on MCF-10A cells. EGF and TGF alpha, two other EGFR ligands, promote important SerpinB5 phosphorylation. Interestingly, EGF treatment is followed by SerpinB5 nuclear accumulation. Altogether, these data indicate that SerpinB5 expression and phosphorylation are developmentally regulated. In vitro analyses indicate that SerpinB5 phosphorylation is regulated by EGFR ligands, but EGF appears to be the only able to induce SerpinB5 nuclear localization.

Dataset Information

Genistein Directly Represses the Phosphorylation of STAT5 in Lactating Mammary Epithelial Cells.

Publications

Genistein Directly Represses the Phosphorylation of STAT5 in Lactating Mammary Epithelial Cells.

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