← Back to Search
Coordinated Expression Of Extracellular Matrix-degrading Proteinases And Their Inhibitors Regulates Mammary Epithelial Function During Involution
R. Talhouk, M. Bissell, Z. Werb
Published 1992 · Medicine, Biology
Download PDFAnalyze on Scholarcy
Extracellular matrix (ECM) plays an important role in the maintenance of mammary epithelial differentiation in culture. We asked whether changes in mouse mammary specific function in vivo correlate with changes in the ECM. We showed, using expression of beta-casein as a marker, that the temporal expression of ECM-degrading proteinases and their inhibitors during lactation and involution are inversely related to functional differentiation. After a lactation period of 9 d, mammary epithelial cells maintained beta-casein expression up to 5 d of involution. Two metalloproteinases, 72-kD gelatinase (and its 62-kD active form), and stromelysin, and a serine proteinase tissue plasminogen activator were detected by day four of involution, and maintained expression until at least day 10. The expression of their inhibitors, the tissue inhibitor of metalloproteinases (TIMP) and plasminogen activator inhibitor-1, preceded the onset of ECM-degrading proteinase expression and was detected by day two of involution, and showed a sharp peak of expression centered on days 4-6 of involution. When involution was accelerated by decreasing lactation to 2 d, there was an accelerated loss of beta-casein expression evident by day four and a shift in expression of ECM-remodeling proteinases and inhibitors to a focus at 2-4 d of involution. To further extend the correlation between mammary-specific function and ECM remodeling we initiated involution by sealing just one gland in an otherwise hormonally sufficient lactating animal. Alveoli in the sealed gland contained casein for at least 7 d after sealing, and closely resembled those in a lactating gland. The relative expression of TIMP in the sealed gland increased, whereas the expression of stromelysin was much lower than that of a hormone-depleted involuting gland, indicating that the higher the ratio of TIMP to ECM-degrading proteinases the slower the process of involution. To test directly the functional role of ECM-degrading proteinases in the loss of tissue-specific function we artificially perturbed the ECM-degrading proteinase-inhibitor ratio in a normally involuting gland by maintaining high concentrations of TIMP protein with the use of surgically implanted slow-release pellets. In a concentration-dependent fashion, involuting mammary glands that received TIMP implants maintained high levels of casein and delayed alveolar regression. These data suggest that the balance of ECM- degrading proteinases and their inhibitors regulates the organization of the basement membrane and the tissue-specific function of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)
This paper references
Distribu - tion of myoepithelial cells and basement membrane proteins in the resting , pregnant , lactating , and involuting rat mammary gland
F. M. Watt (1982)
In vivo analysis of integrin E~ subnnit function in fibronectin matrix assembly
T. Darribe're (1990)
Electron microscopy of milk secretion in the mammary gland of the C3H/Crgl mouse. III. Cytomorphology of the involuting gland.
S. Wellings (1963)
Autocrine regulation of mammary cell
C. N. Bennett (1990)
Ovarian plasminogen activator: Relationship to ovulation and hormonal regulation
W. Beers (1975)
Elvax 40P implants: Sustained
G. B. Silberstein (1982)
Posttranscriptional regulation of cellular gene expression by the c-myc oncogene.
G. Prendergast (1989)
Molecular Cloning: A Lab
J. Sambrook (1989)
A novel regulatory mechanism for whey acidic protein gene expression.
L. Chen (1989)
Metalloproteinases and their inhibitors in matrix remodeling.
L. Matrisian (1990)
Extracellular matrix and hormones transcriptionally regulate bovine beta-casein 5' sequences in stably transfected mouse mammary cells.
C. Schmidhauser (1990)
A novel transcriptional enhancer is involved in the prolactin- and extracellular matrix-dependent regulation of beta-casein gene expression.
C. Schmidhauser (1992)
Removal of basement membrane in the involuting breast.
A. Martinez-Hernandez (1976)
Functional interplay between
R. S. Talhouk (1992)
R. J. RicHes (1988)
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
P. Chomczyński (1987)
Regulation of rat mammary gene expression by extracellular matrix components.
J. L. Blum (1987)
A novel transcriptional enhancer is involved in the prolactin and ECMdependent regulation of/3-casein gone expression
C Schmidhauser (1992)
Functional interplay between extracellular matrix and extracellular matrix-degrading proteinases in the mammary gland: a coordinate system for regulating mammary epithelial function
R. Talhouk (1992)
Molecular cloning of complementary DNA to mouse tissue plasminogen activator mRNA and its expression during F9 teratocarcinoma cell differentiation.
R. Rickles (1988)
Proteinases of the mammary gland: developmental regulation in vivo and vectorial secretion in culture.
R. Talhouk (1991)
Mammary gland involution
G. H. Schmidt (1971)
Calcium-dependent and calcium-independent gelatinolytic proteinase activities of the rat ventral prostate and its secretion: characterization and effect of castration and testosterone treatment.
M. Wilson (1991)
Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development.
C. A. Brenner (1989)
Investigation of mouse mammary
G. B. Silberstein (1987)
Functional interplay between ECM and ECM-degrading proteinases in the mammary gland: a coordinate system for regulating mammary epithelial function
R. S. Talhouk (1992)
Distribution of myoepithelial cells and basement membrane proteins in the resting, pregnant, lactating, and involuting rat mammary gland.
M. Warburton (1982)
Cell culture models of differentiation
F. Watt (1991)
Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane.
M. Barcellos-Hoff (1989)
Expression of extracellular matrix
C. H. Streuli (1990)
Molecular Cloning: A Laboratory Manual
J. Sambrook (1983)
Metalloproteinases and their inhibitors in matrix remodelling . Trends Goner
L M Matrisian (1990)
Mammary gland function during involution.
W. Hurley (1989)
Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland
G. Silberstein (1990)
D. Hamer (1977)
Ultrastrnctural changes accompany
R. J. Richards (1971)
Expression pattern of a gene for a secreted metalloproteinase during late stages of tumor progression
L. Ostrowski (1988)
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
Andrew P. Feinberg (1983)
Control of mammary epithe
C. H. Streuli (1991)
Extracelinlar matrix metaUoproteinases in tumor invasion and metastasis
G. I. Goldberg (1991)
Cell-associated plasminogen activation: regulation and physiological functions.
O. Saksela (1988)
Characterization and expression of a murine gene homologous to human EPA/TIMP: a virus‐induced gene in the mouse.
D. Gewert (1987)
Effects of inhibition of basement membrane collagen deposition on rat mammary gland development.
M. Wicha (1980)
Ultrastrnctural changes accompanying involution of the mammary gland in the rat
R. J. RicHes (1971)
Ultrastrnctural changes accompanying involution of the mammary gland in the rat
R J Richards (1971)
Metalloproteinases mediate extracellular matrix degradation by cells from mouse blastocyst outgrowths.
O. Behrendtsen (1992)
Enhanced synthesis and secretion of type IV collagen and entactin during adipose conversion of 3T3-L1 cells and production of unorthodox laminin complex.
Y. Aratani (1988)
Elvax 40P implants: sustained, local release of bioactive molecules influencing mammary ductal development.
G. Silberstein (1982)
Control of mammary epithelial differentiation: basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity
C. Streuli (1991)
The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium.
A. Howlett (1993)
Functional interplay between ECM and ECM - degrading proteinases in the mammary gland : a coordinate system for regulating mammary epithelial function
T. Fleming (1992)
Growth and differentiation of mammary glands
I. A. Forsyth (1982)
Cell-associated plasminogen activation
O. Saksela (1988)
Electron microscopy of milk secretion in the mammary gland of the C3H/Crgl mouse. I. Cytomorphology of the prelactating and the lactating gland.
S. Wellings (1960)
Expression of extracellular matrix components is regulated by substratum
C. Streuli (1990)
Inhibition of mouse mammary ductal morphogenesis and down-regulation of the EGF receptor by epidermal growth factor.
S. Coleman (1990)
Structure-function relationships in the collagenase family member transin.
R. Sánchez-López (1988)
Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells.
M. Li (1987)
Investigation of mouse mammary ductal growth regulation using slow-release plastic implants.
G. Silberstein (1987)
CHAPTER FOUR – Involution of the Mammary Gland
A. Lascelles (1978)
Designer microenvironments for the analysis of cell and tissue function.
A. Stoker (1990)
A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas
P. Basset (1990)
A novel transcriptional enhancer is involved in the prolactin and ECM - dependent regulation of / 3 - casein gone expression
G. H. Schmidt (1992)
Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory. Cold Spring Harbor
J Sambrook (1988)
Mammary function during the nonlactating period: enzyme, lactose, protein concentrations, and pH of mammary secretions.
W. Hurley (1987)
The role of interstitial collagens in cleft formation of mouse embryonic submandibular gland during initial branching.
Y. Fukuda (1988)
Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue.
C. Monteagudo (1990)
Electron microscopy of milk secre
S. R. Wellings (1963)
This paper is referenced by
Extracellular matrix alters epithelial differentiation.
E. Hay (1993)
Apoptosis in the mammary gland and breast cancer
H. A. Hahm (1998)
CHAPTER 9 – MECHANICAL AND CHEMICAL DETERMINANTS OF TISSUE DEVELOPMENT
D. Ingber (2000)
Modeling Brk/PTK6 Expression in the Mammary Epithelium
Kristopher A. Lofgren (2010)
Lactational competence and involution of the mouse mammary gland require plasminogen.
L. Lund (2000)
Developmental changes in the protein and mRNA content of a p115/transcytosis-associated protein in the bovine mammary gland.
A. Watanabe (2000)
Basement Membrane and Repair of Injury to Peripheral Nerve: Defining a Potential Role for Macrophages, Matrix Metalloproteinases, and Tissue Inhibitor of Metalloproteinases-1
Monique La Fleur (1996)
Fine mapping of quantitative trait Loci on bovine chromosome 6 affecting calving difficulty.
H. Olsen (2008)
The effect of equine metabolic syndrome on the ovarian follicular environment.
D. R. Sessions-Bresnahan (2014)
Molecular portfolios: cells interacting with matrix in repairing airway epithelium
P. Lackie (2008)
Cell–matrix interactions during development and apoptosis of the mouse mammary gland in vivo
Janine M Prince (2002)
Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3.
R. S. Chapman (1999)
Influence of microenvironment on mammary epithelial cell survival in primary culture
D. Blatchford (1999)
The role of matrix metalloproteinases in tumor angiogenesis and tumor metastasis
A. John (2009)
Molecular mechanisms of “detachment-induced apoptosis—Anoikis”
J. Grossmann (2004)
Clinical implications of matrix metalloproteinases
M. Mandal (2004)
The Cancer Degradome
D. Edwards (2008)
ADAM17 co-purifies with TIMP-3 and modulates endothelial invasion responses in three-dimensional collagen matrices.
Hyeong-il Kwak (2009)
Maternal hypoxia increases the activity of MMPs and decreases the expression of TIMPs in the brain of neonatal rats
W. Tong (2010)
Tissue inhibitor of metalloproteinase-2 stimulates mesenchymal growth and regulates epithelial branching during morphogenesis of the rat metanephros.
J. Barasch (1999)
Integrins, adhesion and apoptosis.
J. Meredith (1997)
Identification of promoter activity and differential expression of transcripts encoding the murine stromelysin-1 gene in renal cells.
J. Yee (1997)
Functional role of matrix metalloproteinases (MMPs) in mammary epithelial cell development
P. P. Lee (2001)
Anti‐inflammatory activity of Eugenia punicifolia extract on muscular lesion of mdx dystrophic mice
P. E. Leite (2010)
Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations That Leads to Stable Epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells
A. Lochter (1997)
Lactation status influences expression of CCAAT/enhancer binding protein isoform mRNA in the mouse mammary gland
A. Gigliotti (1998)
Chromogranin A alters ductal morphogenesis and increases deposition of basement membrane components by mammary epithelial cells in vitro.
J. Soriano (1999)
The dominance of the microenvironment in breast and ovarian cancer.
C. Roskelley (2002)
Chapter Fifteen – Mechanochemical Control of Cell Fate Switching
D. Ingber (2007)
Wounds: Biology, Pathology, and Management
H. P. Lorenz (2008)
Microenvironment of the Involuting Mammary Gland Mediates Mammary Cancer Progression
P. Schedin (2007)
Tissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of expression and biological functions.
D. T. Denhardt (1993)See more