MEN1/Menin regulates milk protein synthesis through mTOR signaling in mammary epithelial cells

Li, Honghui; Li, Xue; Wang, Zhonghua; Lin, Xueyan; Yan, Zhiying; Cao, Qiaoqiao; Zhao, Meng; Shi, Kerong

doi:10.1038/s41598-017-06054-w

Cited by 23 publications

(37 citation statements)

References 36 publications

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“…The PI3K/Akt signaling pathway has effects on regulating mammary gland development [41,42]. There are some studies that show that the activation of the PI3K/Akt signaling pathway may enhance mammogenesis and lactogensis [43,44]. According to the previous studies, we found that LA could activate the PI3K/Akt signaling pathway during HC11 differentiation.…”

Section: Discussionmentioning

confidence: 57%

Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice

Yang

et al. 2020

Animals

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Our previous studies demonstrated that lauric acid (LA) stimulated mammary gland development during puberty. However, the roles of LA on lactation in mice remain indeterminate. Thus, the aim of this study was to investigate the effects of dietary LA supplementation on lactation functioning and to study the potential mechanisms during lactation. in vivo, there was no effect of 1% LA dietary supplementation during lactation on the feed intake or body weight of breast-feeding mice. However, maternal LA supplementation significantly expanded the number of mammary gland alveoli of mice during lactation and the average body weight of the offspring, suggesting that LA supplementation enhanced the development and lactation function of the mammary glands. in vitro, 100 μM of LA significantly increased the content of triglycerides (TG) in the cell supernatant of induced HC11 cells, however, with no effect on the expression of the genes associated with fatty acid synthesis. LA also activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. LA dietary supplementation significantly expanded the serum levels of lipid metabolites, including sphingomyelin and other metabolites with the sn-2 position of C12 and sn-1 position of C18 in the TG of the lactating mice. Taken together, dietary supplementation of LA during lactation could promote the lactation function of mice, which might be related to increasing the development of the mammary glands and alternation of serum lipid metabolites. These findings provided more theoretical and experimental basis for the application of lauric acid in the development of mammary glands and lactation function of lactating animals.

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Section: Discussionmentioning

confidence: 57%

Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice

Yang

et al. 2020

Animals

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“…Within the mammary gland, menin was recently found to directly interact with estrogen receptor-α (ERα) in a hormone-dependent manner in breast cancer cells [ 10 ], thereby regulating the transcription of estrogen-responsive genes in these cells [ 11 ]. This finding indicated an important mediator role of menin in mammary gland tissue of dairy cows [ 12 ]. Moreover, loss of heterozygosity of MEN1 was found to cause inherited breast-ovarian cancer in humans [ 13 ] and hyperplasia of breast (female) and prostate (male) cells in mice [ 9 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Menin Modulates Mammary Epithelial Cell Numbers in Bovine Mammary Glands Through Cyclin D1

Shi

et al. 2017

J Mammary Gland Biol Neoplasia

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Menin, the protein encoded by the MEN1 gene, is abundantly expressed in the epithelial cells of mammary glands. Here, we found MEN1/menin expression slowly decreased with advancing lactation but increased by the end of lactation. It happened that the number of bovine mammary epithelial cells decreases since lactation, suggesting a role of menin in the control of mammary epithelial cell growth. Indeed, reduction of menin expression through MEN1-specific siRNA transfection in the bovine mammary epithelial cells caused cell growth arrest in G1/S phase. Decreased mRNA and protein expression of Cyclin D1 was observed upon MEN1 knockdown. Furthermore, menin was confirmed to physically bind to the promoter region of Cyclin D1 through a ChIP assay, indicating that menin plays a regulatory role in mammary epithelial cell cycle progression. Moreover, lower expression of MEN1/menin induced increased epithelial cell apoptosis and caused extracellular matrix remodeling by down-regulating its associated genes, such as DSG2 and KRT5, suggesting that menin’s role may also be involved in the control of cell–cell adhesion in normal mammary glands. Taken together, our data revealed an unknown molecular function of menin in epithelial cell proliferation, which may be important in the regulation of lactation behavior of mammary glands.Electronic supplementary materialThe online version of this article (10.1007/s10911-017-9385-8) contains supplementary material, which is available to authorized users.

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“…The AA sensory function of the mTOR pathway was first demonstrated in a study of hepatocyte autophagy by Blommaart et al [8], who showed that addition of AA inhibited valine release as a result of autophagic protein degradation and the effect was inhibited by rapamycin. Recently, the mTOR pathway has been shown to be critical for AA sensing and utilization in the lactating bovine or mouse MG [9,10].…”

Section: Introductionmentioning

confidence: 99%

AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

Cai

Wang

Zhao

et al. 2020

J Animal Sci Biotechnol

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Background: The local supply of energy-yielding nutrients such as glucose seems to affect the synthesis of milk components in the mammary gland (MG). Thus, our study was conducted to investigate the effects of locally available MG glucose supply (LMGS) on amino acid (AA) sensing and utilization in the MG of lactating dairy goats. Six dosages of glucose (0, 20, 40, 60, 80, and 100 g/d) were infused into the MG through the external pudendal artery to investigate the dose-dependent changes in mammary AA uptake and utilization (Exp.1) and the changes in mRNA and protein expression of the AMPK-mTOR pathway (Expt.2). Results: In Exp.1, total milk AA concentration was highest when goats were infused with 60 g/d glucose, but lower when goats were infused with 0 and 100 g/d glucose. Increasing LMGS quadratically changed the percentages of α S2-casein and α-lactalbumin in milk protein, which increased with infusions from 0 to 60 g/d glucose and then decreased with infusions between 60 and 100 g/d glucose. The LMGS changed the AA availability and intramammary gland AA utilization, as reflected by the mammary AA flux indexes. In Exp.2, the mRNA expression of LALBA in the MG increased quadratically with increasing LMGS, with the highest expression at dose of 60 g/d glucose. A high glucose dosage (100 g/d) activated the general control nonderepressible 2 kinase, an intracellular sensor of AA status, resulting in a reduced total milk AA concentration. Conclusions: Our new findings suggest that the lactating MG in dairy goats may be affected by LMGS through regulation of the AA sensory pathway, AA utilization and protein synthesis, all being driven by the AMPK-mTOR pathway.

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MEN1/Menin regulates milk protein synthesis through mTOR signaling in mammary epithelial cells

Cited by 23 publications

References 36 publications

Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice

Effects of Dietary Supplementation of Lauric Acid on Lactation Function, Mammary Gland Development, and Serum Lipid Metabolites in Lactating Mice

Menin Modulates Mammary Epithelial Cell Numbers in Bovine Mammary Glands Through Cyclin D1

AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats

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