scholarly journals Id4 Regulates Mammary Epithelial Cell Growth and Differentiation and Is Overexpressed in Rat Mammary Gland Carcinomas

2003 ◽  
Vol 163 (6) ◽  
pp. 2495-2502 ◽  
Author(s):  
Liang Shan ◽  
Minshu Yu ◽  
Cunping Qiu ◽  
Elizabeth G. Snyderwine
Keyword(s):  
Mammary Gland ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Cell Growth And Differentiation ◽  
Rat Mammary Gland

Nulliparous CCAAT/Enhancer Binding Proteinδ (C/EBPδ) Knockout Mice Exhibit Mammary Gland Ductal Hyperlasia

2003 ◽  
Vol 228 (3) ◽  
pp. 278-285 ◽  
Author(s):  
Andrew P. Gigliotti ◽  
Peter F. Johnson ◽  
Esta Sterneck ◽  
James W. DeWille
Keyword(s):  
Mammary Gland ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Growth Control ◽  
Mammary Epithelial ◽  
Estrus Cycle ◽  
The Mean ◽  
Cell Growth Control

CCAAT/Enhancer binding proteins (C/EBPs) are a family of nuclear proteins that function in the control of cell growth, death, and differentiation. We previously reported that C/EBPδ plays a key role in mammary epithelial cell G0 growth arrest. In this report, we investigated the role of C/EBPδ in mammary gland development and function using female mice homozygous for a targeted deletion of C/EBPδ (C/EBPδ –/–). C/EBPδ –/– females develop normally and exhibit normal reproductive and lactational performance. Adult nulliparous C/EBPδ –/– females, however, exhibit mammary epithelial cell growth control defects. The mean number of mammary ductal branches is significantly higher in adult nulliparous C/EBPδ –/– females compared with C/EBPδ +/+ (wild-type control) females (66.8 ± 5.2 vs 42.9 * 6.3 branch points/field, P < 0.01). In addition, the mean total mammary gland cellular volume occupied by epithelium is significantly higher in adult nulliparous C/EBPδ –/– females compared with C/EBPδ +/+ controls (29.0± 1.4 vs 20.4 ± 1.3, P < 0.001). Our results showed that the BrdU labeling index was significantly higher in mammary epithelial cells from nulliparous C/EBPδ –/– females compared with C/EBPδ +/+ controls during the proestrus/estrus (4.55 ± 0.70 vs 2.14 ± 0.43, P < 0.01) and metestrus/diestrus (6.92 ± 0.75 vs 3.98 ± 0.43 P < 0.01) phases of the estrus cycle. In contrast, the percentage of mammary epithelial cells undergoing apoptosis during both phases of the estrus cycle did not differ between C/EBPδ –/– and C/EBPδ +/+ females. The increased epithelial cell content and proliferative capacity was restricted to the nulliparous C/EBPδ –/– females as no differences in mammary gland morphology, ductal branching or total epithelial content were observed between multiparous C/EBPδ –/– and C/EBPδ +/+ females. These results demonstrate that C/EBPδ plays a novel role in mammary epithelial cell growth control that appears to be restricted to the nulliparous mammary gland.

Respiration of epithelial component of mammary gland slices

1960 ◽  
Vol 199 (6) ◽  
pp. 1067-1069 ◽  
Author(s):  
E. Douglas Rees
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Biological Parameters ◽  
Hydroxyproline Content ◽  
Epithelial Proliferation ◽  
Cell Component ◽  
Rat Mammary Gland

The respiration of slices from rat mammary gland was accounted for by the independent contributions of each of the three major components of mammary tissue: adipose, epithelial and connective. The contribution of each component was the amount of the component times its characteristic qo2. In the virgin mammary gland the adipose and connective tissue components accounted for the bulk of the observed respiration; but the qo2 increased directly and linearly with epithelial proliferation induced by various means—pregnancy, lactation, or administration of progesterone or estradiol-17ß. An equation containing only biological parameters and relating qo2 to hydroxyproline content of mammary gland was derived. A qo2 value of 14.2 ± 1.8 for the mammary epithelial cell component was obtained.

scholarly journals CLOCK regulates mammary epithelial cell growth and differentiation

2016 ◽  
Vol 311 (6) ◽  
pp. R1125-R1134 ◽  
Author(s):  
Theresa Casey ◽  
Jennifer Crodian ◽  
Aridany Suárez-Trujillo ◽  
Emily Erickson ◽  
Bethany Weldon ◽  
...  
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Serum Starvation ◽  
Epithelial Cell Line ◽  
Wild Type ◽  
Physiological Processes ◽  
Qpcr Analysis ◽  
Cell Growth And Differentiation

Circadian clocks influence virtually all physiological processes, including lactation. Here, we investigate the role of the CLOCK gene in regulation of mammary epithelial cell growth and differentiation. Comparison of mammary morphology in late-pregnant wild-type and ClockΔ19 mice, showed that gland development was negatively impacted by genetic loss of a functional timing system. To understand whether these effects were due, in part, to loss of CLOCK function in the gland, the mouse mammary epithelial cell line, HC11, was transfected with short hairpin RNA that targeted Clock (shClock). Cells transfected with shClock expressed 70% less Clock mRNA than wild-type (WT) HC11 cultures, which resulted in significantly depressed levels of CLOCK protein ( P < 0.05). HC11 lines carrying shClock had four-fold higher growth rates ( P < 0.05), and the percentage of cells in G1 phase was significantly higher (90.1 ± 1.1% of shClock vs. 71.3 ± 3.6% of WT-HC11) following serum starvation. Quantitative-PCR (qPCR) analysis showed shClock had significant effects ( P < 0.0001) on relative expression levels of Ccnd1, Wee1, and Tp63. qPCR analysis of the effect of shClock on Fasn and Cdh1 expression in undifferentiated cultures and cultures treated 96 h with dexamethasone, insulin, and prolactin (differentiated) found levels were reduced by twofold and threefold, respectively ( P < 0.05), in sh Clock line relative to WT cultures. Abundance of CDH1 and TP63 proteins were significantly reduced in cultures transfected with sh Clock. These data support how CLOCK plays a role in regulation of epithelial cell growth and differentiation in the mammary gland.

scholarly journals Tyrosine Phosphorylation of Grb2: Role in Prolactin/Epidermal Growth Factor Cross Talk in Mammary Epithelial Cell Growth and Differentiation

2009 ◽  
Vol 29 (10) ◽  
pp. 2505-2520 ◽  
Author(s):  
Eric Haines ◽  
Parham Minoo ◽  
Zhenqian Feng ◽  
Nazila Resalatpanah ◽  
Xin-Min Nie ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Cell Growth ◽  
Epithelial Cell ◽  
Epidermal Growth Factor ◽  
Tyrosine Phosphorylation ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Cell Growth And Differentiation ◽  
Epidermal Growth

ABSTRACT Characterizing mechanisms regulating mammary cell growth and differentiation is vital, as they may contribute to breast carcinogenesis. Here, we examine a cross talk mechanism(s) downstream of prolactin (PRL), a primary differentiation hormone, and epidermal growth factor (EGF), an important proliferative factor, in mammary epithelial cell growth and differentiation. Our data indicate that EGF exerts inhibitory effects on PRL-induced cellular differentiation by interfering with Stat5a-mediated gene expression independent of the PRL-proximal signaling cascade. Additionally, our data show that PRL is a potent inhibitor of EGF-induced cell proliferation. We identify tyrosine phosphorylation of the growth factor receptor-bound protein 2 (Grb2) as a critical mechanism by which PRL antagonizes EGF-induced cell proliferation by attenuating the activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. Together, our results define a novel negative cross-regulation between PRL and EGF involving the Jak2/Stat5a and Ras/MAPK pathways through tyrosine phosphorylation of Grb2.

scholarly journals The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells

Development ◽  
2001 ◽  
Vol 128 (16) ◽  
pp. 3117-3131 ◽  
Author(s):  
Marina Simian ◽  
Yohei Hirai ◽  
Marc Navre ◽  
Zena Werb ◽  
Andre Lochter ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Growth Factors ◽  
Growth Factor ◽  
Epithelial Cell ◽  
Fibroblast Growth Factor ◽  
Mammary Epithelial Cell ◽  
Three Dimensional ◽  
Branching Morphogenesis ◽  
Mammary Epithelial ◽  
Fibroblast Growth

The mammary gland develops its adult form by a process referred to as branching morphogenesis. Many factors have been reported to affect this process. We have used cultured primary mammary epithelial organoids and mammary epithelial cell lines in three-dimensional collagen gels to elucidate which growth factors, matrix metalloproteinases (MMPs) and mammary morphogens interact in branching morphogenesis. Branching stimulated by stromal fibroblasts, epidermal growth factor, fibroblast growth factor 7, fibroblast growth factor 2 and hepatocyte growth factor was strongly reduced by inhibitors of MMPs, indicating the requirement of MMPs for three-dimensional growth involved in morphogenesis. Recombinant stromelysin 1/MMP3 alone was sufficient to drive branching in the absence of growth factors in the organoids. Plasmin also stimulated branching; however, plasmin-dependent branching was abolished by both inhibitors of plasmin and MMPs, suggesting that plasmin activates MMPs. To differentiate between signals for proliferation and morphogenesis, we used a cloned mammary epithelial cell line that lacks epimorphin, an essential mammary morphogen. Both epimorphin and MMPs were required for morphogenesis, but neither was required for epithelial cell proliferation. These results provide direct evidence for a crucial role of MMPs in branching in mammary epithelium and suggest that, in addition to epimorphin, MMP activity is a minimum requirement for branching morphogenesis in the mammary gland.

scholarly journals Evaluation of different methods to obtain primary mammary epithelial cell cultures from canine spontaneous mammary gland tumors

2013 ◽  
Vol 7 (Suppl 2) ◽  
pp. P41
Author(s):  
Luciana B Gentile ◽  
Márcia K Nagamine ◽  
Isis P Jesus ◽  
Fábio T Toyota ◽  
Adriana T Nishiya ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Cell Cultures ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Epithelial Cell Cultures ◽  
Mammary Gland Tumors ◽  
Primary Mammary Epithelial Cell

scholarly journals The bovine mammary gland expresses multiple functional isoforms of serotonin receptors

2009 ◽  
Vol 203 (1) ◽  
pp. 123-131 ◽  
Author(s):  
Laura L Hernandez ◽  
Sean W Limesand ◽  
Jayne L Collier ◽  
Nelson D Horseman ◽  
Robert J Collier
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Mrna Expression ◽  
Mammary Epithelial Cell ◽  
Caspase 3 ◽  
Mammary Epithelial ◽  
Bovine Mammary Gland ◽  
Functional Activities ◽  
Receptor Isoforms ◽  
Human And Mouse

Recent studies in dairy cows have demonstrated that serotonergic ligands affect milk yield and composition. Correspondingly, serotonin (5-HT) has been demonstrated to be an important local regulator of lactational homeostasis and involution in mouse and human mammary cells. We determined the mRNA expression of bovine 5-HT receptor (HTR) subtypes in bovine mammary tissue (BMT) and used pharmacological agents to evaluate functional activities of 5-HT receptors. The mRNAs for five receptor isoforms (HTR1B, 2A, 2B, 4, and 7) were identified by conventional real-time (RT)-PCR, RT quantitative PCR, and in situ hybridization in BMT. In addition to luminal mammary epithelial cell expression, HTR4 was expressed in myoepithelium, and HTR1B, 2A, and 2B were expressed in small mammary blood vessels. Serotonin suppressed milk protein mRNA expression (α-lactalbumin and β-casein mRNA) in lactogen-treated primary bovine mammary epithelial cell (BMEC) cultures. To probe the functional activities of individual receptors, caspase-3 activity and expression of α-lactalbumin and β-casein were measured. Both SB22489 (1B antagonist) and ritanserin (2A antagonist) increased caspase-3 activity. Expression of α-lactalbumin and β-casein mRNA levels in BMEC were stimulated by low concentrations of SB224289, ritanserin, or pimozide. These results demonstrate that there are multiple 5-HT receptor isoforms in the bovine mammary gland, and point to profound differences between serotonergic systems of the bovine mammary gland and the human and mouse mammary glands. Whereas human and mouse mammary epithelial cells express predominately the protein for the 5-HT7 receptor, cow mammary epithelium expresses multiple receptors that have overlapping, but not identical, functional activities.

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