Milk protein expression and ductal morphogenesis in the mammary gland in vitro: Hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction

1987 ◽  
Vol 120 (1) ◽  
pp. 245-258 ◽  
Author(s):  
Darrell Wiens ◽  
Chung S. Park ◽  
Frank E. Stockdale
Keyword(s):  
Mammary Gland ◽  
Epithelial Cell ◽  
Protein Expression ◽  
Mammary Epithelial Cell ◽  
Milk Protein ◽  
Cell Interaction ◽  
Mammary Epithelial ◽  
Ductal Morphogenesis

Mammary epithelial cell differentiation in vitro is regulated by an interplay of EGF action and tenascin-C downregulation

1995 ◽  
Vol 108 (6) ◽  
pp. 2445-2456 ◽  
Author(s):  
G. Wirl ◽  
M. Hermann ◽  
P. Ekblom ◽  
R. Fassler
Keyword(s):  
Mammary Gland ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Potent Inducer ◽  
Tenascin C ◽  
Epithelial Cell Differentiation

Expression of the extracellular matrix glycoprotein tenascin-C in the mammary gland is associated with cellular proliferation and cell motility during organogenesis and tumorigenesis. Because the source and the regulation of tenascin-C in these tissues are unclear, we have used tenascin-C cDNA, FITC-immunofluorescence and immuno-precipitation to examine tenascin-C expression of mammary epithelial cells. Using several mammary epithelial cell lines we could show that tenascin-C can be produced and secreted by epithelial cells. However it was found that tenascin-C synthesis was inversely correlated with the polarized epithelial phenotype. Among three mouse mammary epithelial cell clones, tenascin-C expression was most abundant in HC-11 cells, the least differentiated cell type. Expression levels were high during the growth phase but were nearly abolished when cells were grown to confluence and induced to express milk proteins. Downregulation of tenascin-C by EGF apparently commits HC-11 cells to respond to lactogenic hormones and consequently, hormone induced levels of beta-casein mRNA decreased significantly when HC-11 cells were grown on a tenascin-C substrate. On the other hand, TGF-beta, another growth factor involved in coordinated growth and differentiation of the mammary gland in vivo was found to be a very potent inducer of tenascin-C. The generation of fully polarized and tight epithelium affected the levels of tenascin-C expression. In contrast to HC-11 cells, which do not form epithelial domes in vitro, highly polarized and dome forming EpH4 and Fos-ER cells nearly lacked tenascin-C. Similarly, induction of dome formation in the rat mammary stem cell line Rama 25 by the differentiation inducer dimethylsulfoxide caused a loss of TN-C-transcripts. The inability of Fos-ER cells to develop domes in the presence of soluble tenascin-C also suggests its interference with induction and maintenance of mammary epithelial cell differentiation.

Bisphenol A and benzophenone-3 exposure alters milk protein expression and its transcriptional regulation during functional differentiation of the mammary gland in vitro

2020 ◽  
Vol 191 ◽  
pp. 110185
Author(s):  
Gabriela A. Altamirano ◽  
Ayelen L. Gomez ◽  
Gonzalo Schierano-Marotti ◽  
Mónica Muñoz-de-Toro ◽  
Horacio A. Rodriguez ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Mammary Gland ◽  
Bisphenol A ◽  
Protein Expression ◽  
Milk Protein ◽  
Functional Differentiation

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.

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