Cell Shape and Integrin Signaling Regulate the Differentiation State of Mammary Epithelial Cells

  • Aruna Somasiri
  • Calvin D. Roskelley
Part of the Methods in Molecular Biology book series (MIMB, volume 129)


When they are cultured on a reconstituted basement membrane gel, mammary epithelial cells round-up, aggregate, form cell-cell junctions, and undergo an apical/basal polarization that ultimately produces a central lumen. The resulting three-dimensional ‘mammospheres’ closely resemble lactational alveoli in vivo and they fully differentiate when they are maintained in an appropriate mileau of lactogenic hormones. Specifically, the cells express milk protein genes, package the products in secretory vesicles, transport the vesicles to the apical cell surface, and release the products into the central lumen. Therefore, dynamic and reciprocal interactions between epithelial cells and the surrounding basement membrane are key regulators of phenotypic change in the developing mammary gland (1, 2, 3, 4).


Basement Membrane Lactogenic Hormone Mammary Epithelial Cell Differentiation Medium Central Lumen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Bissell, M. J., Hall, G. J., and Parry, G. (1982). How does the extracellular matrix direct gene expression? J. Theor. Biol. 99, 31–68.PubMedCrossRefGoogle Scholar
  2. 2.
    Barcellos-Hoff, M. H., Aggler, J., Ram, T. G., and Bissell, M. J. (1989) Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development 105, 223–235.PubMedGoogle Scholar
  3. 3.
    Aggeler, J., Ward, J., Blackie, L. M., Barcellos-Hoff, M. H., Streuli, C. H., and Bissell, M. J. (1991) Cytodifferentiation of mouse mammary epithelial cells cultured on a reconstituted basement membrane reveals striking similarities to development in vivo. J. Cell Sci. 99, 407–417.PubMedGoogle Scholar
  4. 4.
    Howlett, A. R. and Bissell, M. J. (1993) The influence of tissue microenvironment on the development and function of mammary epithelium. Epith. Cell Biol. 2, 79–89.Google Scholar
  5. 5.
    Roskelley, C. D., Srebrow, A., and Bissell, M. J. (1995). A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression. Curr. Opin. Cell Biol. 7, 736–747.PubMedCrossRefGoogle Scholar
  6. 6.
    Desprez, P. Y., Roskelley, C. D., and Bissell, M. J. (1993). Isolation of functional cell lines from a mouse mammary epithelial cell strain: the importance of basement membrane and cell-cell interactions. Mol. Cell. Differ. 1, 99–110.Google Scholar
  7. 7.
    Close, M. J., Howlett, A. R., Roskelley, C. D., Desprez, P. Y., Bailey, N., Rowning, B., Teng, C. T., Stampfer, M. R., and Yaswen, P. (1997). Lactoferrin expression in mammary epithelial cells is mediated by changes in cell shape and actin cytoskeleton. J. Cell Sci. 110, 2861–2871.PubMedGoogle Scholar
  8. 8.
    Roskelley, C. D., Desprez, P. Y., and Bissell, M. J. (1994). Extracellular matrix-dependent tissue-specific gene expression in mammary epithelial cells requires both physical and biochemical signal transduction. Proc. Natl. Acad. Sci. USA 91, 12,378–12,382.PubMedCrossRefGoogle Scholar
  9. 9.
    Roskelley, C. D. and Bissell, M. J. (1995). Dynamic reciprocity revisited: a continuous, bidirectional flow of information between cells and the extracellular matrix regulates mammary epithelial cell function. Biochem. Cell Biol. 73, 391–397.PubMedCrossRefGoogle Scholar
  10. 10.
    Streuli, C. H., Bailey, N., and Bissell, M. J. (1991) Control of mammary epithelial differentiation: the separate roles of cell-substratum and cell-cell interaction. J. Cell Biol. 115, 1383–1385.PubMedCrossRefGoogle Scholar
  11. 11.
    Streuli, C. H., Schmidhauser, C., Bailey, N., Yurchenco, P., Skubitz, P. N., Roskelley, C. D., and Bissell, M. J. (1995a). Laminin mediates tissue-specific gene expression in mammary epithelia. J. Cell Biol. 129, 591–603.PubMedCrossRefGoogle Scholar
  12. 12.
    Schmidhauser, C., Bissell, M. J., Myers, C. A., and Casperson, G. F. (1990). Extracellular matrix and hormones transcriptionally regulate bovine b-casein 5′ sequences in stably transfected mouse mammary cells. Proc. Natl. Acad. Sci. USA 87, 9118–9122.PubMedCrossRefGoogle Scholar
  13. 13.
    Danielson, K. G., Oborn, C. J., Durban, E. M., Butel, J. S., and Medina, D. (1984) Epithelial mouse mammary cell line exhibiting normal morphogenesis in vivo and functional differentiation in vitro. Proc. Natl. Acad. Sci. USA 81, 3756–3760.PubMedCrossRefGoogle Scholar
  14. 14.
    Ball, R. K., Friis, R. R., Schoenenberger, C. A., Doppler, W., and Groner, B. (1988) Prolactin regulation of β-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial cell line. EMBO J. 7, 2089–2095.PubMedGoogle Scholar
  15. 15.
    Reichman, E., Ball, R., Groner, B., and Friis, R. R. (1989) New mammary epithelial and fibroblastic cell clones in coculture form structures competent to differentiate functionally. J. Cell Biol. 108, 1127–1138.CrossRefGoogle Scholar
  16. 16.
    Doppler, W., Welte, T., and Philipp, S. (1995) CCAAT/enhancer-binding protein isoforms are expressed in mammary epithelial cells and bind to multiple sites in the β-casein promoter. J. Biol. Chem 270, 17,962–17,969.PubMedCrossRefGoogle Scholar
  17. 17.
    Streuli, C. H., Edwards, G. M., Delcommenne, M., Whitelaw, C. B., Burdon, T. G., Schindler, C., and Watson, C. J. (1995b) Stat5 as a target for regulation by the extracellular matrix. J. Biol. Chem. 270, 21,639–21,644.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  • Aruna Somasiri
    • 1
  • Calvin D. Roskelley
    • 1
  1. 1.Department of AnatomyUniversity of British ColumbiaVancouverCanada

Personalised recommendations