scholarly journals The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2-dependent mechanism, and controls cell proliferation and apoptosis of mammary epithelial cells

Oncogene ◽  
2007 ◽  
Vol 26 (44) ◽  
pp. 6431-6441 ◽  
Author(s):  
N Wang ◽  
K K Lin ◽  
Z Lu ◽  
K S Lam ◽  
R Newton ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Proliferation And Apoptosis ◽  
Dependent Mechanism

scholarly journals p19ARFDetermines the Balance between Normal Cell Proliferation Rate and Apoptosis during Mammary Gland Development

2004 ◽  
Vol 15 (5) ◽  
pp. 2302-2311 ◽  
Author(s):  
Yijun Yi ◽  
Anne Shepard ◽  
Frances Kittrell ◽  
Biserka Mulac-Jericevic ◽  
Daniel Medina ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mammary Gland ◽  
Epithelial Cells ◽  
Protein Level ◽  
Normal Cell ◽  
Mammary Gland Development ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Proliferation Rate ◽  
Gland Development

This study demonstrated, for the first time, the following events related to p19ARFinvolvement in mammary gland development: 1) Progesterone appears to regulate p19ARFin normal mammary gland during pregnancy. 2) p19ARFexpression levels increased sixfold during pregnancy, and the protein level plateaus during lactation. 3) During involution, p19ARFprotein level remained at high levels at 2 and 8 days of involution and then, declined sharply at day 15. Absence of p19ARFin mammary epithelial cells leads to two major changes, 1) a delay in the early phase of involution concomitant with downregulation of p21Cip1and decrease in apoptosis, and 2) p19ARFnull cells are immortal in vivo measured by serial transplantion, which is partly attributed to complete absence of p21Cip1compared with WT cells. Although, p19ARFis dispensable in mammary alveologenesis, as evidenced by normal differentiation in the mammary gland of pregnant p19ARFnull mice, the upregulation of p19ARFby progesterone in the WT cells and the weakness of p21Cip1in mammary epithelial cells lacking p19ARFstrongly suggest that the functional role(s) of p19ARFin mammary gland development is critical to sustain normal cell proliferation rate during pregnancy and normal apoptosis in involution possibly through the p53-dependent pathway.

RagD regulates amino acid mediated-casein synthesis and cell proliferation via mTOR signalling in cow mammary epithelial cells

2018 ◽  
Vol 85 (2) ◽  
pp. 204-211 ◽  
Author(s):  
Ying Mu ◽  
Dongmei Zheng ◽  
Cong Wang ◽  
Wei Yu ◽  
Xiaonan Zhang
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Lactation Period ◽  
Mtor Inhibition ◽  
Pregnancy And Lactation ◽  
Casein Synthesis

This research paper addresses the hypothesis that RagD is a key signalling factor that regulates amino acid (AA) mediated-casein synthesis and cell proliferation in cow mammary epithelial cells (CMECs). The expression of RagD was analysed at different times during pregnancy and lactation in bovine mammary tissue from dairy cows. We showed that expression of RagD at lactation period was higher (P < 0·05) than that at pregnancy period. When CMECs were treated with methionine (Met) or lysine (Lys), expression of RagD, β-casein (CSN2), mTOR and p-mTOR, and cell proliferation were increased. Further, when CMECs were treated to overexpress RagD, expression of CSN2, mTOR and p-mTOR, and cell proliferation were up-regulated. Furthermore, the increase in expression of CSN2, mTOR and p-mTOR, and cell proliferation in response to Met or Lys supply was inhibited by inhibiting RagD, and those effects were reversed in the overexpression model. When CMECs were treated with RagD overexpression together with mTOR inhibition or conversely with RagD inhibition together with mTOR overexpression, results showed that the increase in expression of CSN2 and cell proliferation in response to RagD overexpression was prevented by inhibiting mTOR, and those effects were reversed by overexpressing mTOR. The interaction of RagD with subunit proteins of mTORC1 was analysed, and the result showed that RagD interacted with Raptor. CMECs were treated with Raptor inhibition, and the result showed that the increase in expression of mTOR and p-mTOR in response to RagD overexpression was inhibited by inhibiting Raptor.In conclusion, our study showed that RagD is an important activation factor of mTORC1 in CMECs, activating AA-mediated casein synthesis and cell proliferation, potentially acting via Raptor.

scholarly journals IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1

2021 ◽  
Vol 22 (21) ◽  
pp. 12008
Author(s):  
Wan-Ju Wu ◽  
Sue-Hong Wang ◽  
Chun-Chi Wu ◽  
Yi-An Su ◽  
Chin-Yin Chiang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Prolonged Treatment ◽  
Signaling Crosstalk ◽  
Promote Cell Proliferation ◽  
Primary Mouse ◽  
Cytokine Milieu

T helper (Th)2 cytokines such as interleukin (IL)-4 and IL-13 control immune function by acting on leukocytes. They also regulate multiple responses in non-hematopoietic cells. During pregnancy, IL-4 and IL-13 facilitate alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts and requires substantial cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we demonstrate that IL-4 and IL-13 promote cell proliferation, leading to enlargement of mammary acini with partially filled lumens. The mitogenic effects of IL-4 and IL-13 are mediated by STAT6 as inhibition of STAT6 suppresses cell proliferation and improves lumen formation. In addition, IL-4 and IL-13 stimulate tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Prolonged treatment with these cytokines leads to increased IRS-1 abundance, which, in turn, amplifies IL-4- and IL-13-stimulated IRS-1 tyrosine phosphorylation. Through signaling crosstalk between IL-4/IL-13 and insulin, a hormone routinely included in mammary cultures, IRS-1 tyrosine phosphorylation is further enhanced. Lowering IRS-1 expression reduces cell proliferation, suggesting that IRS-1 is involved in IL-4- and IL-13-stimulated cell proliferation. Thus, a Th2-dominant cytokine milieu during pregnancy confers mammary gland development by promoting cell proliferation.

scholarly journals Transcriptional Repression of MFG-E8 Causes Disturbance in the Homeostasis of Cell Cycle Through DOCK/ZP4/STAT Signaling in Buffalo Mammary Epithelial Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Arvind K. Verma ◽  
Syed A. Ali ◽  
Parul Singh ◽  
Sudarshan Kumar ◽  
Ashok K. Mohanty
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Epithelial Cells ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Bovine Milk ◽  
Mammary Epithelial ◽  
Directed Network ◽  
Ideal System

The mammary gland is a unique apocrine gland made up of a branching network of ducts that end in alveoli. It is an ideal system to study the molecular mechanisms associated with cell proliferation, differentiation, and oncogenesis. MFG-E8, also known as Lactadherin, is a vital glycoprotein related to the milk fat globule membrane and initially identified to get secreted in bovine milk. Our previous report suggests that a high level of MFG-E8 is indicative of high milk yield in dairy animals. Here, we showed that MFG-E8 controls the cell growth and morphology of epithelial cells through a network of regulatory transcription factors. To understand the comprehensive action, we downregulated its expression in MECs by MFG-E8 specific shRNA. We generated a knockdown proteome profile of differentially expressed proteins through a quantitative iTRAQ experiment on a high-resolution mass spectrometer (Q-TOF). The downregulation of MFG-E8 resulted in reduced phagocytosis and cell migration ability, whereas it also leads to more lifespan to knockdown vis-a-vis healthy cells, which is confirmed through BrdU, MTT, and Caspase 3/7. The bioinformatics analysis revealed that MFG-E8 knockdown perturbs a large number of intracellular signaling, eventually leading to cessation in cell growth. Based on the directed network analysis, we found that MFG-E8 is activated by CX3CL1, TP63, and CSF2 and leads to the activation of SOCS3 and CCL2 for the regulation of cell proliferation. We further proved that the depletion of MFG-E8 resulted in activated cytoskeletal remodeling by MFG-E8 knockdown, which results in the activation of three independent pathways ZP4/JAK-STAT5, DOCK1/STAT3, and PIP3/AKT/mTOR. Overall, this study suggests that MFG-E8 expression in mammary epithelial cells is an indication of intracellular deterioration in cell health. To date, to the best of our knowledge, this is the first study that explores the downstream targets of MFG-E8 involved in the regulation of mammary epithelial cell health.

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