Online citations, reference lists, and bibliographies.
← Back to Search

New Mammary Epithelial And Fibroblastic Cell Clones In Coculture Form Structures Competent To Differentiate Functionally

E. Reichmann, R. Ball, B. Groner, R. Friis
Published 1989 · Medicine, Biology

Cite This
Download PDF
Analyze on Scholarcy
Share
We have established and characterized a spontaneously immortalized, nontumorigenic mouse mammary cell line, designated IM-2. IM-2 cells synthesize large amounts of the milk protein beta-casein upon addition of lactogenic hormones. The induction of beta-casein occurs rapidly and does not require any exogenous extracellular matrix components. The IM- 2 cell line is morphologically heterogeneous and could be separated into cell clones with epithelial and fibroblastic characteristics. In monoculture, none of the epithelial clones could be induced to synthesize caseins. Coculture of epithelial and fibroblastic clones, however, rendered the epithelial cells competent to differentiate functionally; the addition of lactogenic hormones to these cocultures resulted in the synthesis of beta-casein in amounts comparable to that seen with the original IM-2 line. Using this unique cell system, we have investigated the interrelationships between different steps in differentiation leading to hormone-induced casein production. Independent of hormones, epithelial-fibroblastic cell contacts led to the formation of characteristic structures showing the deposition of laminin. We found that the epithelial cells located in these structures also exhibited significantly increased levels of cytokeratin intermediate filament polypeptides. Double immunofluorescence revealed that the cells inducible by hormones to synthesize casein, colocalized exactly with the areas of laminin deposition and with the cells showing greatly intensified cytokeratin expression. These results suggest that hormone-independent differentiation events take place in response to intercellular epithelial-mesenchymal contacts. These events in turn bring about a state of competence for functional differentiation after lactogenic hormonal stimulation.
This paper references
10.1021/BI00591A005
Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
J. Chirgwin (1979)
10.1152/PHYSREV.1980.60.4.1049
Multiple hormone interactions in the developmental biology of the mammary gland.
Y. J. Topper (1980)
10.1016/0014-4827(82)90231-2
Growth of mouse mammary gland end buds cultured in a collagen gel matrix.
J. Richards (1982)
Disruption of the in vivo
Lin (1981)
Understanding breast cancer : clinical and laboratory concepts
M. Rich (1983)
10.1073/PNAS.81.12.3756
Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro.
K. Danielson (1984)
10.1038/283249a0
Intermediate filaments as mechanical integrators of cellular space
E. Lazarides (1980)
Vesicular stomatitis virus infects and matures only through the basolateral surface of the polarized epithelial cell line
S D Fuller (1984)
Cell-cell interactions promote mam
J. F. Levine (1985)
10.1073/PNAS.82.5.1419
Interaction of mouse mammary epithelial cells with collagen substrata: regulation of casein gene expression and secretion.
E. Lee (1985)
10.1073/PNAS.84.1.136
Influence of a reconstituted basement membrane and its components on casein gene expression and secretion in mouse mammary epithelial cells.
M. Li (1987)
The interaction in vitro of the intermediate filament protein vimentin with naturally occurring RNAs and DNAs.
P. Traub (1983)
10.1016/0012-1606(85)90328-8
Expression of keratins and other cytoskeletal proteins in mouse mammary epithelium during the normal developmental cycle and primary culture.
H. Asch (1985)
10.1111/J.1432-1033.1982.TB06660.X
Characterization and cloning of the mRNAs specific for the lactating mouse mammary gland.
L. Hennighausen (1982)
10.1016/0014-4827(81)90435-3
Differences of expression of cytoskeletal proteins in cultured rat hepatocytes and hepatoma cells.
W. Franke (1981)
Prolactin regulation of E-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line
R K Ball (1988)
Epithelial-mesenchymal interactions in mammary gland development and its perturbation in relation to tumorigenesis
T Sakakura (1983)
Maintenance and induction of mor
J. T. Emerman (1977)
10.1016/0092-8674(83)90357-4
Regulation of fibronectin biosynthesis by glucocorticoids in human fibrosarcoma cells and normal fibroblasts
N. Oliver (1983)
Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory
T Maniatis (1982)
10.1111/J.1432-1033.1987.TB13476.X
Laminin-nidogen complex. Extraction with chelating agents and structural characterization.
M. Paulsson (1987)
10.1083/JCB.105.5.2043
Regulation of differentiation and polarized secretion in mammary epithelial cells maintained in culture: extracellular matrix and membrane polarity influences
G. Parry (1987)
10.1083/JCB.102.5.1907
The identification of extracellular matrix (ECM) binding sites on the basal surface of embryonic corneal epithelium and the effect of ECM binding on epithelial collagen production
S. Sugrue (1986)
10.1083/JCB.100.5.1415
Cell-cell interactions promote mammary epithelial cell differentiation
J. F. Levine (1985)
10.1201/9781351073417-9
Laminin--a glycoprotein from basement membranes.
R. Timpl (1979)
10.1016/0003-2697(73)90217-0
A rapid, sensitive, and specific method for the determination of protein in dilute solution.
W. Schaffner (1973)
A clonal
S. M. Campbell (1988)
10.1073/PNAS.80.12.3850
In vivo and in vitro observations on laminin production by Schwann cells.
C. Cornbrooks (1983)
Cytoplasmic microtubules are essential for the formation of membrane-bound polyribosomes.
P. Walker (1985)
Molecular Cloning: A Laboratory Manual
J. Sambrook (1983)
10.1038/291249A0
Intermediate filaments in 3T3 cells collapse after intracellular injection of a monoclonal anti-intermediate filament antibody
M. Klymkowsky (1981)
10.1073/PNAS.69.6.1408
Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose.
H. Aviv (1972)
Cytochalasin released mRNA
D. A. Ornelles (1986)
Acad. Sci. USA
10.1016/0092-8674(84)90440-9
Construction and applications of a highly transmissible murine retrovirus shuttle vector
C. Cepko (1984)
10.1128/MCB.6.5.1650
Cytochalasin releases mRNA from the cytoskeletal framework and inhibits protein synthesis.
D. Ornelles (1986)
10.1002/j.1460-2075.1988.tb03048.x
Prolactin regulation of beta‐casein gene expression and of a cytosolic 120‐kd protein in a cloned mouse mammary epithelial cell line.
R. Ball (1988)
10.1093/JNCI/76.6.1143
Properties of mouse mammary epithelial cell lines characterized by in vivo transplantation and in vitro immunocytochemical methods.
D. Medina (1986)
Factors affecting the differentiation of epithelial transport and responsiveness to hormones.
J. Handler (1984)
vivo and in vitro observations on laminin production by Schwann cells. Proc. Natl. Acad. Sci. USA
C J Cornhrooks (1983)
10.1083/JCB.99.4.1424
Differential control of cytokeratins and vimentin synthesis by cell- cell contact and cell spreading in cultured epithelial cells
A. Ben-Ze’ev (1984)
10.1002/IJC.2910180415
Markers to distinguish normal and neoplastic mammary epithelial cells in vitro: comparison of saturation density, morphology and concanavalin a reactivity
B. Voyles (1976)
10.1016/0092-8674(88)90056-6
Role of laminin a chain in the development of epithelial cell polarity
G. Klein (1988)
Role of Laminin
Klein (1988)
Epithelial-mesenchymal interactions in the production of basement membrane components in the gut.
P. Simon-Assmann (1988)
10.1016/0092-8674(84)90527-0
Vesicular stomatitis virus infects and matures only through the basolateral surface of the polarized epithelial cell line, MDCK
S. Fuller (1984)
Epithelial-mesenchymal interactions in mammary gland
T. Sakakura (1983)
Characterization and cloning
L. G. Hennighausen (1982)
10.1002/JCP.1041350103
Role of the cytoskeleton in laminin induced mammary gene expression
J. L. Blum (1988)
10.1083/JCB.99.4.1541
Electrical currents flow out of domes formed by cultured epithelial cells
K. Sugahara (1984)
10.1083/JCB.91.3.827
Characterization of a myoepithelial cell line derived from a neonatal rat mammary gland
M. Warburton (1981)
10.1038/227680A0
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
U. Laemmli (1970)
10.1016/0022-1759(77)90177-6
A sensitive radioimmunoassay for a component of mouse casein.
J. Enami (1977)
10.1016/0092-8674(81)90514-6
Disruption of the in vivo distribution of the intermediate filaments in fibroblasts through the microinjection of a specific monoclonal antibody
J. Lin (1981)
Cell surface proteoglycan
A. Rapraeger (1986)
10.1016/0014-4827(88)90029-8
A clonal derivative of mammary epithelial cell line COMMA-D retains stem cell characteristics of unique morphological and functional heterogeneity.
S. M. Campbell (1988)
10.1073/PNAS.76.3.1323
Inducers of mammalian cell differentiation stimulate dome formation in a differentiated kidney epithelial cell line (MDCK).
Julia E. Lever (1979)
10.1083/JCB.100.4.1209
Effect of viral infection on host protein synthesis and mRNA association with the cytoplasmic cytoskeletal structure
A. M. Bonneau (1985)
10.1146/ANNUREV.CB.01.110185.001331
Cell surface polarity in epithelia.
K. Simons (1985)
10.1016/0165-022X(84)90040-X
Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose.
J. Kyhse-Andersen (1984)
10.1016/0092-8674(77)90176-3
High resolution two-dimensional electrophoresis of basic as well as acidic proteins
P. Z. O'Farrell (1977)
High resolution two-dimensional electrophoresis of proteins.
P. O'Farrell (1975)
Neurite outgrowth promoting factors in conditioned medium are complexes containing laminin
A. D. Lander (1985)
10.1083/JCB.103.6.2683
Cell surface proteoglycan associates with the cytoskeleton at the basolateral cell surface of mouse mammary epithelial cells
A. Rapraeger (1986)
10.1083/JCB.92.3.665
Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization
E. Lane (1982)
10.1073/PNAS.73.11.4041
Tissue interaction in androgen response of embryonic mammary rudiment of mouse: identification of target tissue for testosterone.
K. Kratochwil (1976)
10.1073/PNAS.79.10.3213
Extracellular matrix promotes mammary epithelial growth and differentiation in vitro.
M. Wicha (1982)
10.1073/PNAS.84.4.935
Sequence of the cDNA encoding the laminin B1 chain reveals a multidomain protein containing cysteine-rich repeats.
M. Sasaki (1987)
10.1083/JCB.101.3.976
Heparan sulfate proteoglycans from mouse mammary epithelial cells: localization on the cell surface with a monoclonal antibody
M. Jalkanen (1985)
10.1016/0022-2836(81)90326-0
Shapes, domain organizations and flexibility of laminin and fibronectin, two multifunctional proteins of the extracellular matrix.
J. Engel (1981)
10.1016/0012-1606(85)90456-7
Comparative analysis of casein synthesis during mammary cell differentiation in collagen and mammary gland development in vivo.
E. Durban (1985)
10.1016/0012-1606(87)90122-9
Milk protein expression and ductal morphogenesis in the mammary gland in vitro: hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction.
D. Wiens (1987)
Shapes, domain organizations
J. Engel (1981)



This paper is referenced by
10.1007/s00441-016-2415-9
Identification of a shootin1 isoform expressed in peripheral tissues
Yasuna Higashiguchi (2016)
Sustained activation of STAT 5 is essential for chromatin remodeling and maintenance of mammary-specifi c function
R. Xu ()
10.1007/BFB0031032
Regulation of gene expression by prolactin.
W. Doppler (1994)
10.1083/JCB.131.4.1095
Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland
Z. Feng (1995)
10.1186/1471-2121-10-85
Disruption of occludin function in polarized epithelial cells activates the extrinsic pathway of apoptosis leading to cell extrusion without loss of transepithelial resistance
N. Beeman (2009)
Microenvironmental regulation of epithelial-mesenchymal transition
Qike K Chen (2013)
10.1016/0012-1606(90)90302-Y
Induction of the endogenous whey acidic protein (Wap) gene and a Wap-myc hybrid gene in primary murine mammary organoids.
C. Schoenenberger (1990)
Role of cell type-specific promoters in the developmental regulation of T1, an interleukin 1 receptor homologue.
E. Thomassen (1995)
10.1007/978-1-4615-1973-7_30
Basement Membrane in the Control of Mammary Gland Function
C. Streuli (1995)
10.1016/J.CCR.2006.04.023
Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance.
V. Fantin (2006)
10.1007/978-1-4615-3940-7_5
The insulin-like growth factors, their receptors, and their binding proteins in human breast cancer.
D. Yee (1991)
10.3168/JDS.S0022-0302(95)76662-0
Subcloning the MAC-T bovine mammary epithelial cell line: morphology, growth properties, and cytogenetic analysis of clonal cells.
B. Zavizion (1995)
10.1016/S0014-5793(98)00348-2
1,25‐Dihydroxyvitamin D3 inhibits tenascin‐C expression in mammary epithelial cells
J. M. González-Sancho (1998)
10.1152/ajpendo.00200.2014
Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development.
Abby L. Johnson (2014)
10.1016/j.diff.2013.03.003
Extracellular matrix proteins regulate epithelial-mesenchymal transition in mammary epithelial cells.
Qike K Chen (2013)
10.1016/B978-0-12-397175-3.00046-6
Lactation and Its Hormonal Control
S. Anderson (2015)
10.1016/j.cell.2006.06.043
ZO-1 and ZO-2 Independently Determine Where Claudins Are Polymerized in Tight-Junction Strand Formation
Kazuaki Umeda (2006)
10.4161/cc.9.21.13578
Laminin regulates PI3K basal localization and activation to sustain STAT5 activation
R. Xu (2010)
10.1126/science.7531366
Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix
N. Boudreau (1995)
10.1023/A:1018719612087
β1,4-Galactosyltransferase and Lactose Biosynthesis: Recruitment of a Housekeeping Gene from the Nonmammalian Vertebrate Gene Pool for a Mammary Gland Specific Function
N. Shaper (2004)
Regulation of ABCG2 Expression in the Lactating Mammary Gland
Alex Man Lai Wu (2014)
10.1290/1071-2690(2000)036<0578:MFSGAM>2.0.CO;2
MAMMARY FIBROBLASTS STIMULATE GROWTH, ALVEOLAR MORPHOGENESIS, AND FUNCTIONAL DIFFERENTIATION OF NORMAL RAT MAMMARY EPITHELIAL CELLS
Kathleen M. Darcy (2000)
Contribution of SETD7 methyltransferase to cell proliferation and differentiation
Inês A. Batista (2016)
10.1002/JCB.240560219
Negative regulatory element in the mammary specific whey acidic protein promoter
A. Kolb (1994)
10.1007/978-1-4615-3500-3_20
Stromal-epithelial interactions in breast cancer.
K. Cullen (1992)
10.1083/JCB.131.6.1573
Hepatocyte growth factor/scatter factor induces a variety of tissue- specific morphogenic programs in epithelial cells
V. Brinkmann (1995)
10.1083/JCB.140.5.1039
Rab17 Regulates Membrane Trafficking through Apical Recycling Endosomes in Polarized Epithelial Cells
P. Zacchi (1998)
MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition.
J. Pinkas (2002)
10.1074/jbc.M703037200
Signaling Pathways Regulating TC21-induced Tumorigenesis*
M. Erdogan (2007)
Epidermal growth factor receptor, platelet-derived growth factor receptor, and c-erbB-2 receptor activation all promote growth but have distinctive effects upon mouse mammary epithelial cell differentiation.
D. Taverna (1991)
10.1139/O99-010
Plasticity of mammary epithelia during normal development and neoplastic progression.
A. Lochter (1998)
10.1016/B978-0-12-386986-9.00002-8
Monoclonal antibodies as novel neurotherapeutic agents in CNS injury and repair.
Aruna Sharma (2012)
See more
Semantic Scholar Logo Some data provided by SemanticScholar