Regulation of mammary epithelial cell function: a role for stromal and basement membrane matrices

PROTOPLASMA ◽  
1990 ◽  
Vol 159 (2-3) ◽  
pp. 85-95 ◽  
Author(s):  
A. R. Howlett ◽  
Mina J. Bissell
Keyword(s):  
Epithelial Cell ◽  
Basement Membrane ◽  
Mammary Epithelial Cell ◽  
Cell Function ◽  
Mammary Epithelial

scholarly journals Suppression of mammary epithelial cell differentiation by the helix-loop-helix protein Id-1.

1995 ◽  
Vol 15 (6) ◽  
pp. 3398-3404 ◽  
Author(s):  
P Y Desprez ◽  
E Hara ◽  
M J Bissell ◽  
J Campisi
Keyword(s):  
Transcription Factors ◽  
Mammary Gland ◽  
Epithelial Cell ◽  
Basement Membrane ◽  
Mammary Epithelial Cell ◽  
Three Dimensional ◽  
Mammary Epithelial ◽  
Epithelial Cell Line ◽  
Helix Loop Helix ◽  
Beta Casein

Cell proliferation and differentiation are precisely coordinated during the development and maturation of the mammary gland, and this balance invariably is disrupted during carcinogenesis. Little is known about the cell-specific transcription factors that regulate these processes in the mammary gland. The mouse mammary epithelial cell line SCp2 grows well under standard culture conditions but arrests growth, forms alveolus-like structures, and expresses beta-casein, a differentiation marker, 4 to 5 days after exposure to basement membrane and lactogenic hormones (differentiation signals). We show that this differentiation entails a marked decline in the expression of Id-1, a helix-loop-helix (HLH) protein that inactivates basic HLH transcription factors in other cell types. SCp2 cells stably transfected with an Id-1 expression vector grew more rapidly than control cells under standard conditions, but in response to differentiation signals, they arrested growth and formed three-dimensional structures similar to those of control cells. Id-1-expressing cells did not, however, express beta-casein. Moreover, 8 to 10 days after receiving differentiation signals, they lost three-dimensional organization, invaded the basement membrane, and then resumed growth. SCp2 cells expressing an Id-1 antisense vector grew more slowly than controls; in response to differentiation signals, they remained stably growth arrested and fully differentiated, as did control cells. We suggest that Id-1 renders cells refractory to differentiation signals and receptive to growth signals by inactivating one or more basic HLH proteins that coordinate growth and differentiation in the mammary epithelium.

Dynamic reciprocity revisited: a continuous, bidirectional flow of information between cells and the extracellular matrix regulates mammary epithelial cell function

1995 ◽  
Vol 73 (7-8) ◽  
pp. 391-397 ◽  
Author(s):  
C. D. Roskelley ◽  
M. J. Bissell
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Cell Function ◽  
Mammary Epithelium ◽  
Mammary Epithelial ◽  
Biochemical Signals ◽  
Bidirectional Flow ◽  
Flow Of Information

Interactions between cells and the extracellular matrix (ECM) generate two classes of signals, mechanical and biochemical. In the case of the mammary epithelial cell, both are required to initiate ECM-dependent expression of the abundant milk protein β-casein. Mechanical signals induce a cellular rounding, while functional biochemical signals are associated with an increase in tyrosine phosphorylation. These individual components are part of a complex signalling hierarchy that leads to the emergence of the fully functional lactational phenotype. Interestingly, both the assembly and disassembly of this hierarchy, which occur cyclically in vivo, are constantly modulated by dynamic and reciprocal interactions that take place within a functional unit composed of both the cell and the ECM.Key words: mammary epithelium, differentiation, extracellular matrix, casein.

scholarly journals A Novel Pathway for Mammary Epithelial Cell Invasion Induced by the Helix-Loop-Helix Protein Id-1

1998 ◽  
Vol 18 (8) ◽  
pp. 4577-4588 ◽  
Author(s):  
Pierre-Yves Desprez ◽  
Claudia Qiao Lin ◽  
Nicole Thomasset ◽  
Carolyn J. Sympson ◽  
Mina J. Bissell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Epithelial Cell ◽  
Basement Membrane ◽  
Human Breast Cancer ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Human Breast ◽  
Helix Loop Helix

ABSTRACT Mammary epithelial cells undergo changes in growth, invasion, and differentiation throughout much of adulthood, and most strikingly during pregnancy, lactation, and involution. Although the pathways of milk protein expression are being elucidated, little is known, at a molecular level, about control of mammary epithelial cell phenotypes during normal tissue morphogenesis and evolution of aggressive breast cancer. We developed a murine mammary epithelial cell line, SCp2, that arrests growth and functionally differentiates in response to a basement membrane and lactogenic hormones. In these cells, expression of Id-1, an inhibitor of basic helix-loop-helix transcription factors, declines prior to differentiation, and constitutive Id-1 expression blocks differentiation. Here, we show that SCp2 cells that constitutively express Id-1 slowly invade the basement membrane but remain anchorage dependent for growth and do not form tumors in nude mice. Cells expressing Id-1 secreted a ∼120-kDa gelatinase. From inhibitor studies, this gelatinase appeared to be a metalloproteinase, and it was the only metalloproteinase detectable in conditioned medium from these cells. A nontoxic inhibitor diminished the activity of this metalloproteinase in vitro and repressed the invasive phenotype of Id-1-expressing cells in culture. The implications of these findings for normal mammary-gland development and human breast cancer were investigated. A gelatinase of ∼120 kDa was expressed by the mammary gland during involution, a time when Id-1 expression is high and there is extensive tissue remodeling. Moreover, high levels of Id-1 expression and the activity of a ∼120-kDa gelatinase correlated with a less-differentiated and more-aggressive phenotype in human breast cancer cells. We suggest that Id-1 controls invasion by normal and neoplastic mammary epithelial cells, primarily through induction of a ∼120-kDa gelatinase. This Id-1-regulated invasive phenotype could contribute to involution of the mammary gland and possibly to the development of invasive breast cancer.

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