scholarly journals Three-Dimensional Scaffolds for Mammary Epithelial Cell Growth

2008 ◽  
Author(s):  
Megan M. Barry
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Three Dimensional ◽  
Mammary Epithelial

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.

scholarly journals Pleiotropic effects of FGFR1 on cell proliferation, survival, and migration in a 3D mammary epithelial cell model

2005 ◽  
Vol 171 (4) ◽  
pp. 663-673 ◽  
Author(s):  
Wa Xian ◽  
Kathryn L. Schwertfeger ◽  
Tracy Vargo-Gogola ◽  
Jeffrey M. Rosen
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Molecular Mechanisms ◽  
Cell Model ◽  
Smooth Muscle Actin ◽  
Three Dimensional ◽  
Mammary Epithelial ◽  
Matrix Metalloproteinase 3

Members of the fibroblast growth factor (FGF) family and the FGF receptors (FGFRs) have been implicated in mediating various aspects of mammary gland development and transformation. To elucidate the molecular mechanisms of FGFR1 action in a context that mimics polarized epithelial cells, we have developed an in vitro three-dimensional HC11 mouse mammary epithelial cell culture model expressing a drug-inducible FGFR1 (iFGFR1). Using this conditional model, iFGFR1 activation in these growth-arrested and polarized mammary acini initially led to reinitiation of cell proliferation, increased survival of luminal cells, and loss of cell polarity, resulting in the disruption of acinar structures characterized by the absence of an empty lumen. iFGFR1 activation also resulted in a gain of invasive properties and the induction of matrix metalloproteinase 3 (MMP-3), causing the cleavage of E-cadherin and increased expression of smooth muscle actin and vimentin. The addition of a pan MMP inhibitor abolished these phenotypes but did not prevent the effects of iFGFR1 on cell proliferation or survival.

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.

Regulation of Mammary Epithelial Cell Growth in Mice and Rats*

1990 ◽  
Vol 11 (4) ◽  
pp. 494-523 ◽  
Author(s):  
WALTER IMAGAWA ◽  
GAUTAM K. BANDYOPADHYAY ◽  
SATYABRATA NANDI
Keyword(s):  
Cell Growth ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial
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