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.

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.

scholarly journals Microarray analysis of RhoC-transformed mammary epithelial cells suggests molecular mechanisms of inflammatory breast cancer

10.1038/87212 ◽  
2001 ◽  
Vol 27 (S4) ◽  
pp. 73-73
Author(s):  
Sofia Merajver ◽  
Zhi-Fen Wu ◽  
Tammy Chang ◽  
Hamid Mirshahidi ◽  
Paul Meltzer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Microarray Analysis ◽  
Inflammatory Breast Cancer ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial

Septin6 regulates cell growth and casein synthesis in dairy cow mammary epithelial cells via mTORC1 pathway

2019 ◽  
Vol 86 (2) ◽  
pp. 181-187
Author(s):  
Bin Li ◽  
Zhuzha Basang ◽  
Lijun Hu ◽  
Liu Liu ◽  
Nan Jiang
Keyword(s):  
Cell Growth ◽  
Epithelial Cells ◽  
Dairy Cow ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Regulatory Factor ◽  
Mtor Inhibition ◽  
Mtorc1 Pathway ◽  
Positive Factor ◽  
Casein Synthesis

AbstractThis research paper addresses the hypothesis that Septin6 is a key regulatory factor influencing amino acid (AA)-mediated cell growth and casein synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were treated with absence of AA (AA−), restricted concentrations of AA (AAr) or normal concentrations of AA (AA+) for 24 h. Cell growth, expression of CSN2 and Septin6 were increased in response to AA supply. Overexpressing or inhibiting Septin6 demonstrated that cell growth, expression of CSN2, mTOR, p-mTOR, S6K1 and p-S6K1 were up-regulated by Septin6. Furthermore, overexpressing or inhibiting mTOR demonstrated that the increase in cell growth and expression of CSN2 in response to Septin6 overexpression were inhibited by mTOR inhibition, and vice versa. Our hypothesis was supported; we were able to show that Septin6 is an important positive factor for cell growth and casein synthesis, it up-regulates AA-mediated cell growth and casein synthesis through activating mTORC1 pathway in DCMECs.

scholarly journals CircRNA8220 Sponges MiR-8516 to Regulate Cell Viability and Milk Synthesis via Ras/MEK/ERK and PI3K/AKT/mTOR Pathways in Goat Mammary Epithelial Cells

Animals ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1347
Author(s):  
Chao Zhu ◽  
Yue Jiang ◽  
Junru Zhu ◽  
Yonglong He ◽  
Hao Yin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Negative Feedback ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Mammary Epithelial Cells ◽  
Noncoding Rnas ◽  
Mammary Epithelial ◽  
Circular Rnas ◽  
Stanniocalcin 2 ◽  
Goat Mammary Epithelial Cells

Circular RNAs (circRNAs), which are considered a large class of endogenous noncoding RNAs, function as regulators in various biological procedures. In this study, the function and molecular mechanisms of circRNA8220 in goat mammary epithelial cells (GMECs) were explored. CircRNA8220 could spong miR-8516 and block the function of miR-8516 by binding to the target site of miR-8516 a negative feedback relationship existed between circRNA8220 and miR-8516. Stanniocalcin 2 (STC2) was a target gene of miR-8516. circRNA8220 could up-regulate the expression of STC2 by sponging miR-8516 in GMECs. circRNA8220/miR-8516/STC2 could promote proliferation and enhance the synthesis of β-casein and triglycerides (TG) via Ras/MEK/ERK and PI3K/AKT/mTOR signaling pathways, respectively.

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