Skip to main content
SpringerLink
Log in

Three-dimensional mammary primary culture model systems

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Model systems have been developed to investigate the complex and coordinated regulation of mammary gland development and transformation. Primary cultures, using newly isolated cells or tissue, are optimal for such studies since, in comparison to immortalized cell lines, the normal signal transduction pathways are prsumed to be intact. Three such models are described, including whole organ culture, mammary epithelial cell (MEC) organoids, and MEC-stromal cocultures. Studies using whole-organ culture have the advantage that the normal glandular architecture remains intact, the MEC can undergo lobuloalveolar development and express milk proteins in a hormone dependent manner, and, following hormonal withdrawal, undergo involution. Moreover, transformation of the MEC is readily accomplished. Culture of isolated MEC organoids within an EHS-derived reconstituted basement membrane permits extensive proliferation, branching end bud and alveolar morphogenesis, and accumulation of milk protein and lipid in a physiologically relevant hormone- and growth factor-dependent manner. This model can thus be utilized to investigate the mechanism by which various modulators exert their direct effects on the epithelium. Finally, in view of compelling evidence for stromal-epithelial interactions during normal mammary gland development, and potentially also during the development of malignancy, models in which MEC can be cocultured with enriched populations of stroma offer considerable potential as a tool to understand the nature and mechanisms of the interactions that occur during the various developmental states, and how such interactions may go awry during carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J. M. Rosen, R. Humphreys, S. Krnacik, P. Juo, and B. Raught (1994). The regulation of mammary gland development by hormones, growth factors, and oncogenes.Prog. Clin. Biol. Res. 38795–111.

    PubMed  Google Scholar 

  2. B. Groner, S. Altiok, and V. Meier (1994). Hormonal regulation of transcription factor activity in mammary epithelial cells.Mol. Cell. Endocrinol. 100109–114.

    Article  PubMed  Google Scholar 

  3. C. S. Lee and T. Oka (1992). A pregnancy-specific mammary nuclear factor involved in the repression of the mouse β-casein gene transcription by progesterone.J. Biol. Chem. 2675797–5801.

    PubMed  Google Scholar 

  4. M. R. Banerjee, M. Antoniou, J. B. Joshi, and P. K. Majumder (1983). Recent advances in hormonal regulation of milk protein gene expression. In M. A. Rich, J. C. Hager, and P. Furmanski (eds.),Understanding Breast Cancer: Clinical and Laboratory Concepts, Marcel Dekker, New York, pp. 335–363.

    Google Scholar 

  5. F. Gouilleux, H. Wakao, M. Mundt, and B. Groner (1994). Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription.EMBO J. 134361–4369.

    PubMed  Google Scholar 

  6. H. Wakao, F. Gouilleux, and B. Groner (1994). Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response.EMBO J. 132182–2191.

    PubMed  Google Scholar 

  7. J. Russo, B. A. Gusterson, A. E. Rogers, I. H. Russo, S. R. Wellings, and M. J. Van Zwieten (1990). Comparative study of human and rat mammary tumorigenesis.Lab. Invest. 62244–278.

    PubMed  Google Scholar 

  8. W. Imagawa, J. Yang, R. Guzman, and S. Nandi (1994). Control of mammary gland development. In E. Knobil and J. D. Neill (eds.),The Physiology of Reproduction, Raven Press, New York, Chapter 56, pp. 1033–1063.

    Google Scholar 

  9. M. H. Barcellos-Hoff and M. J. Bissell (1989). Mammary epithelial cells as a model for studies of the regulation of gene expression. In K. S. Matlin and J. D. Valentich (eds.),Functional Epithelial Cells in Culture, Alan R. Liss, New York, pp. 399–433.

    Google Scholar 

  10. K. G. Danielson, C. J. Oborn, E. M. Durban, J. S. Butel, and D. Medina (1984). Epithelial mouse mammary cell line exhibiting normal morphogenesisin vivo and functional differentiationin vitro.Proc. Natl. Acad. Sci. USA 813756–3760.

    PubMed  Google Scholar 

  11. R. K. Ball, R. R. Friis, C. A. Schoenenberger, W. Doppler, and B. Groner (1988). Prolactin regulation of β-casein gene expression and of a cytosolic 120-kd protein in a cloned mouse mammary epithelial line.EMBO J. 72089–2095.

    PubMed  Google Scholar 

  12. C. Schmidhauser, M. J. Bissell, C. A. Myers, and G. F. Casperson (1990). Extracellular matrix and hormones transcriptionally regulate bovine β-casein 5′ sequences in stably transfected mouse mammary cells.Proc. Natl. Acad. Sci. USA 879118–9122.

    PubMed  Google Scholar 

  13. P. S. Rudland (1987). Stem cells and the development of mammary cancers in experimental rats and in humans.Cancer Metastasis Rev. 655–83.

    Article  PubMed  Google Scholar 

  14. M. R. Banerjee (1976). Responses of mammary cells to hormones.Int. Rev. Cytol. 471–97.

    PubMed  Google Scholar 

  15. W. Imagawa, G. K. Bandyopadhyay, and S. Nandi (1990). Regulation of mammary epithelial cell growth in mice and rats.Endocrine Rev. 11494–523.

    Google Scholar 

  16. M. R. Banerjee and M. Antoniou (1984). Serum-free culture of the isolated whole mammary organ of the mouse: A model for the study of differentiation and carcinogenesis. In D. W. Barnes, D. A. Sirbasku, and G. H. Sato (eds.),Methods for Serum-Free Culture of Cells of the Endocrine System. Alan R. Liss, New York, Chapter 9, pp. 143–169.

    Google Scholar 

  17. J. M. Rosen, J. R. Rodgers, C. H. Couch, C. A. Bisbee, Y. David-Inouye, S. M. Campbell, and L.-Y. Yu-Lee (1986). Multihormonal regulation of milk protein gene expression.Ann. N.Y. Acad. Sci. 47863–76.

    PubMed  Google Scholar 

  18. M. R. Banerjee, S. Chakraborty, D. Kinder, K. Manoharan, and R. Menon (1987). Cell biology of mouse mammary carcinogenesis in organ culture. In D. Medina, W. Kidwell, G. Heppner, and E. Anderson (eds.),Cellular and Molecular Biology of Mammary Cancer, Plenum Press, New York, pp. 353–379.

    Google Scholar 

  19. Y. Yang, E. Spitzer, N. Kenney, W. Zschiesche, M. Li, A. Kromminga, T. Müller, F. Spener, A. Lezius, J. H. Veerkamp, G. H. Smith, D. S. Salomon, and R. Grosse (1994). Members of the fatty acid binding protein family are differentiation factors for the mammary gland.J. Cell Biol. 1271097–1109.

    Article  PubMed  Google Scholar 

  20. R. R. Ichinose and S. Nandi (1966). Influence of hormones on lobulo-alveolar differentiation of mouse mammary glandsin vitro.J. Endocrinol. 35331–340.

    PubMed  Google Scholar 

  21. Q. J. Tonelli and S. Sorof (1980). Epidermal growth factor requirement for development of cultured mammary gland.Nature 285250–252.

    Article  PubMed  Google Scholar 

  22. R. W. Turkington (1969). The role of epithelial growth factor in mammary gland developmentin vitro.Exp. Cell Res. 5779–85.

    Article  PubMed  Google Scholar 

  23. A. A. Hobbs, D. A. Richards, D. J. Kessler, and J. M. Rosen (1982). Complex hormonal regulation of rat casein gene expression.J. Biol. Chem. 2573598–3605.

    PubMed  Google Scholar 

  24. M. Yoshimura and T. Oka (1990). Hormonal induction of β-casein gene expression: Requirement of ongoing protein synthesis for transcription.Endocrinology 126427–433.

    PubMed  Google Scholar 

  25. P. Chomczynski, P. Qasba, and Y. J. Topper (1986). Transcriptional and posttranscriptional roles of glucocorticoid in the expression of the rat 25,000 molecular weight casein gene.Biochem. Biophys. Res. Commun. 134812–818.

    Article  PubMed  Google Scholar 

  26. B. K. Vonderhaar and K. L. Nakhasi (1986). Bifunctional activity of epidermal growth factor on alpha- and kappa-casein gene expression in rodent mammary glandsin vitro.Endocrinology 1191178–1184.

    PubMed  Google Scholar 

  27. L. Sankaran and Y. J. Topper (1987). Is EGF a physiological inhibitor of mouse mammary casein synthesis? Unphysiological responses to pharmacological levels of hormones.Biochem. Biophys. Res. Commun. 146121–125.

    Article  PubMed  Google Scholar 

  28. W. R. Kidwell, M. Bano, and D. S. Salomon (1984). Growth of normal mammary epithelium on collagen in serum-free medium. In D. W. Barnes, D. A. Sirbasku, and G. H. Sato (eds.),Methods for Serum-Free Culture of Cells of the Endocrine System, Alan R. Liss, New York, Chapter 7, pp. 105–125.

    Google Scholar 

  29. K. M. Darcy, J. D. Black, H. A. Hahm, and M. M. Ip (1991). Mammary organoids from immature virgin rats undergo ductal and alveolar morphogenesis when grown within a reconstituted basement membrane.Exp. Cell Res. 19649–65.

    Article  PubMed  Google Scholar 

  30. H. K. Kleinman, M. L. McGarvey, J. R. Hassell, V. L. Star, F. B. Cannon, G. W. Laurie, and G. M. Martin (1986). Basement membrane complexes with biological activity.Biochemistry 25312–318.

    Article  PubMed  Google Scholar 

  31. M. S. Wicha, G. Lowrie, E. Kohn, P. Bagavandoss, and T. Mahn (1982). Extracellular matrix promotes mammary epithelial growth and differentiationin vitro.Proc. Natl. Acad. Sci. USA 793213–3217.

    PubMed  Google Scholar 

  32. C. J. Wilde, H. R. Hasan, and R. J. Mayer (1984). Comparison of collagen gels and mammary extracellular matrix as substrata for study of terminal differentiation in rabbit mammary epithelial cells.Exp. Cell Res. 151519–532.

    Article  PubMed  Google Scholar 

  33. D. S. Grant, H. K. Kleinman, C. P. Leblond, S. Inoue, A. E. Chung, and G. R. Martin (1985). The basement-membrane-like matrix of the mouse EHS tumor. II. Immunohistochemical quantitation of six of its components.Am. J. Anat. 174387–398.

    Article  PubMed  Google Scholar 

  34. M. M. Ip, S. F. Shoemaker, and K. M. Darcy (1992). Regulation of rat mammary epithelial cell proliferation and differentiation by tumor necrosis factor alpha.Endocrinology 1302833–2844.

    Article  PubMed  Google Scholar 

  35. P.-P. H. Lee, M.-T. Lee, K. M. Darcy, K. Shudo, and M. M. Ip (1995). Modulation of normal mammary epithelial cell proliferation, morphogenesis and functional differentiation by retinoids: A comparison of the retinobenzoic acid derivative RE80 with retinoic acid.Endocrinology 1361707–1717.

    Article  PubMed  Google Scholar 

  36. P.-P. H. Lee, K. M. Darcy, K. Shudo, and M. M. Ip (1995). Interaction of retinoids with steroid and peptide hormones in modulating morphological and functional differentiation of normal rat mammary epithelial cells.Endocrinology 1361718–1730.

    Article  PubMed  Google Scholar 

  37. H. A. Hahm and M. M. Ip (1990). Primary culture of normal rat mammary epithelial cells within a basement membrane matrix. I. Regulation of proliferation by hormones and growth factors.In Vitro Cell. Dev. Biol. 26791–802.

    PubMed  Google Scholar 

  38. J. T. Emerman and D. R. Pitelka (1977). Maintenance and induction of morphological differentiation in dissociated mammary epithelium on floating collagen membranes.In Vitro 13316–328.

    PubMed  Google Scholar 

  39. J. T. Emerman, J. Enami, D. R. Pitelka, and S. Nandi (1977). Hormonal effects on intracellular and secreted casein in cultures of mouse mammary epithelial cells on floating collagen membranes.Proc. Natl. Acad. Sci. USA 744466–4470.

    PubMed  Google Scholar 

  40. J. T. Emerman, S. J. Burwen, and D. R. Pitelka (1979). Substrate properties influencing ultrastructural differentiation of mammary epithelial cells in culture.Tissue Cell 11109–119.

    Article  PubMed  Google Scholar 

  41. J. M. Shannon and D. R. Pitelka (1981). The influence of cell shape on the induction of functional differentiation in mouse mammary cellsin vitro.In Vitro 171016–1028.

    PubMed  Google Scholar 

  42. E. Y.-H. Lee, G. Parry, and M. J. Bissell (1984). Modulation of secreted proteins of mouse mammary epithelial cells by the collagenous substrata.J. Cell Biol. 98146–155.

    Article  PubMed  Google Scholar 

  43. S. P. Ethier (1986). Serum-free culture conditions for the growth of normal rat mammary epithelial cells in primary culture.In Vitro Cell. Dev. Biol. 22485–490.

    PubMed  Google Scholar 

  44. J. Richards, D. Pasco, J. Yang, R. Guzman, and S. Nandi (1983). Comparison of the growth of normal and neoplastic mouse mammary epithelial cells on plastic, on collagen gels and in collagen gels.Exp. Cell Res. 1461–14.

    Article  PubMed  Google Scholar 

  45. Y. M. Suard, M. T. Haeuptle, E. Farinon, and J.-P. Kraehenbuhl (1983). Cell proliferation and milk protein gene expression in rabbit mammary cell cultures.J. Cell Biol. 961435–1442.

    Article  PubMed  Google Scholar 

  46. E. Y.-H. Lee, W.-H. Lee, C. S. Kaetzel, G. Parry, and M. J. Bissell (1985). Interaction of mouse mammary epithelial cells with collagen substrata: Regulation of casein gene expression and secretion.Proc. Natl. Acad. Sci. USA 821419–1423.

    PubMed  Google Scholar 

  47. Q. J. Tonelli and S. Sorof (1982). Induction of biochemical differentiation in three-dimensional collagen cultures of mammary epithelial cells from virgin mice.Differentiation 22195–200.

    PubMed  Google Scholar 

  48. J. Richards, S. Hamamoto, S. Smith, D. Pasco, R. Guzman, and S. Nandi (1983). Response of end bud cells from immature rat mammary gland to hormones when cultured in collagen gel.Exp. Cell Res. 14795–109.

    Article  PubMed  Google Scholar 

  49. M. T. Haeuptle, Y. L. Suard, E. Bogenmann, H. Reggio, L. Racine, and J.-P. Kraehenbuhl (1983). Effect of cell shape change on the function and differentiation of rabbit mammary cells in culture.J. Cell Biol. 961425–1434.

    Article  PubMed  Google Scholar 

  50. E. M. Durban, D. Medina, and J. S. Butel (1985). Comparative analysis of casein synthesis during mammary cell differentiation in collagen and mammary gland developmentin vivo.Dev. Biol. 109288–298.

    Article  PubMed  Google Scholar 

  51. D. Flynn, J. Yang, and S. Nandi (1982). Growth and differentiation of primary cultures of mouse mammary epithelium embedded in collagen gel.Differentiation 22191–194.

    PubMed  Google Scholar 

  52. B. K. Levay-Young, G. K. Bandyopadhyay, and S. Nandi (1987). Linoleic acid, but not cortisol, stimulates accumulation of casein by mouse mammary epithelial cells in serum-free collagen gel culture.Proc. Natl. Acad. Sci. USA 848448–8452.

    PubMed  Google Scholar 

  53. S. Miyamoto, R. C. Guzman, R. C. Osborn, and S. Nandi (1988). Neoplastic transformation of mouse mammary epithelial cells byin vitro exposure toN-methyl-N-nitrosourea.Proc. Natl. Acad. Sci. USA 85477–481.

    PubMed  Google Scholar 

  54. F. S. Kittrell, C. J. Oborn, and D. Medina (1992). Development of mammary preneoplasiasin vivo from mouse mammary epithelial cell linesin vitro.Cancer Res. 521924–1932.

    PubMed  Google Scholar 

  55. J. L. Blum, M. E. Zeigler, and M. S. Wicha (1987). Regulation of rat mammary gene expression by extracellular matrix components.Exp. Cell Res. 173322–340.

    Article  PubMed  Google Scholar 

  56. L.-H. Chen and M. J. Bissell (1989). A novel regulatory mechanism for whey acidic protein gene expression.Cell Regul. 145–54.

    PubMed  Google Scholar 

  57. M. C. Neville, L. Stahl, L. A. Brozo, and J. Lowe-Lieber (1991). Morphogenesis and secretory activity of mouse mammary cultures on EHS biomatrix.Protoplasma 1631–8.

    Article  Google Scholar 

  58. J. Aggeler, J. Ward, L. M. Blackie, M. H. Barcellos-Hoff, C. H. Streuli, and M. J. Bissell (1991). Cytodifferentiation of mouse mammary epithelial cells cultured on a reconstituted basement membrane reveals striking similarities to developmentin vivo.J. Cell Sci. 99407–417.

    PubMed  Google Scholar 

  59. M. H. Barcellos-Hoff, J. Aggeler, T. G. Ram, and M. J. Bissell (1989). Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane.Development 105223–235.

    PubMed  Google Scholar 

  60. H. A. Hahm, M. M. Ip, K. Darcy, J. D. Black, W. K. Shea, S. Forczek, M. Yoshimura, and T. Oka (1990). Primary culture of normal rat mammary epithelial cells within a basement membrane matrix. II. Functional differentiation under serum-free conditions.In Vitro. Cell Dev. Biol. 26803–814.

    PubMed  Google Scholar 

  61. K. M. Darcy, S. F. Shoemaker, P.-P. H. Lee, M. M. Vaughan, J. D. Black, and M. M. Ip (1995). Prolactin and epidermal growth factor regulation of the proliferation, morphogenesis and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture.J. Cell. Physiol. 163346–364.

    Article  PubMed  Google Scholar 

  62. K. M. Darcy, S. F. Shoemaker, P.-P. H. Lee, B.A. Ganis, and M. M. Ip (1995). Hydrocortisone and progesterone regulation of the proliferation, morphogenesis and functional differentiation of normal rat mammary epithelial cells in three dimensional primary culture.J. Cell. Physiol. 163365–379.

    Article  PubMed  Google Scholar 

  63. C. H. Streuli and M. J. Bissell (1990). Expression of extracellular matrix components is regulated by substratum.J. Cell. Biol. 1101405–1415.

    Article  PubMed  Google Scholar 

  64. M. P. Marinkovich and V. Rocha (1986). Collagen synthesis and deposition during mammary epithelial cell spreading on collagen gels.J. Cell. Physiol. 12861–70.

    Article  PubMed  Google Scholar 

  65. G. Parry, E. Y.-H. Lee, D. Farson, M. Koval, and M. J. Bissell (1985). Collagenous substrata regulate the nature and distribution of glycosaminoglycans produced by differentiated cultures of mouse mammary epithelial cells.Exp. Cell Res. 156487–499.

    Article  PubMed  Google Scholar 

  66. M. E. Zeigler and M. S. Wicha (1992). Posttranscriptional regulation of α-casein mRNA accumulation by laminin.Exp. Cell Res. 200481–489.

    Article  PubMed  Google Scholar 

  67. C. H. Streuli, N. Bailey, and M. J. Bissell (1991). Control of mammary epithelial differentiation: Basement membrane induces tissue-specific gene expression in the absence of cell-cell interaction and morphological polarity.J. Cell Biol. 1151383–1395.

    PubMed  Google Scholar 

  68. S. Vukicevic, H. K. Kleinman, F. P. Luyten, A. B. Roberts, N. S. Roche, and A. H. Reddi (1992). Identification of multiple active growth factors in basement membrane matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components.Exp. Cell. Res. 2021–8.

    Article  PubMed  Google Scholar 

  69. H. W. Schnaper, D. S. Grant, W. G. Stetler-Stevenson, R. Fridman, G. D'Orazi, A. N. Murphy, R. E. Bird, M. Hoythya, T. R. Fuerst, D. L. French, J. P. Quigley, and H. K. Kleinman (1993). Type IV collagenase(s) and TIMPs modulate endothelial cell morphogenesisin vitro.J. Cell. Physiol. 156235–246.

    Article  PubMed  Google Scholar 

  70. K. Kratochwil (1987). Epithelium-mesenchyme interaction in the fetal mammary gland. In D. Medina, W. Kidwell, G. Heppner, and E. Anderson (eds.),Cellular and Molecular Biology of Mammary Cancer, Plenum Press, New York, pp. 67–80.

    Google Scholar 

  71. T. Sakakura (1991). New aspects of stroma-parenchyma relations in mammary gland differentiation.Int. Rev. Cytol. 125165–202.

    PubMed  Google Scholar 

  72. G. R. Cunha, P. Young, S. Hamamoto, R. Guzman, and S. Nandi (1992). Developmental response of adult mammary epithelial cells to various fetal and neonatal mesenchymes.Epithelial Cell Biol. 1105–118.

    PubMed  Google Scholar 

  73. E. M. Rivera and S. Vijayaraghavan (1982). Proliferation of ductal outgrowths by carcinogen-induced rat mammary tumors in gland-free mammary fat pads.J. Natl. Cancer Inst. 69517–525.

    PubMed  Google Scholar 

  74. C. W. Welsch, D. H. O'Connor, C. F. Aylsworth, and L. G. Sheffield (1987). Normal but not carcinomatous primary rat mammary epithelium: readily transplanted to and maintained in the athymic nude mouse.J. Natl. Cancer Inst. 78557–565.

    PubMed  Google Scholar 

  75. S. P. Ethier and K. C. Cundiff (1987). Importance of extended growth potential and growth factor independence onin vivo neoplastic potential of primary rat mammary carcinoma cells.Cancer Res. 475316–5322.

    PubMed  Google Scholar 

  76. J. J. DeCosse, C. Gossens, J. F. Kuzman, and B. R. Unsworth (1975). Embryonic inductive tissues that cause histologic differentiation of murine mammary carcinomain vitro.J. Natl. Cancer Inst. 54913–922.

    PubMed  Google Scholar 

  77. K. J. Cullen and M. E. Lippman (1991). Stromal-epithelial interactions in breast cancer. In R. B. Dickson and M. E. Lippman (eds.),Genes, Oncogenes, and Hormones: Advances in Cellular and Molecular Biology of Breast Cancer, Kluwer, Boston, Chapter 20, pp. 413–431.

    Google Scholar 

  78. D. Wiens, C. S. Park, and F. E. Stockdale (1987). Milk protein expression and ductal morphogenesis in the mammary glandin vitro: hormone-dependent and-independent phases of adipocyte-mammary epithelial cell interaction.Dev. Biol. 120245–258.

    Article  PubMed  Google Scholar 

  79. T. Kanazawa and H. L. Hosick (1992). A co-culture system for studies of paracrine effects of stromal cells on the growth of epithelial cells.J. Tiss. Cult. Meth. 1459–62.

    Article  Google Scholar 

  80. P. S. Rudland, A. C. T. Davies, and S.-W. Tsao (1984). Rat mammary preadipocytes in culture produce a trophic agent for mammary epithelial—prostaglandin E2.J. Cell. Physiol. 120364–376.

    Article  PubMed  Google Scholar 

  81. J. C. Beck, H. L. Hosick, and B. A. Watkins (1989). Growth of epithelium from a preneoplastic mammary outgrowth in response to mammary adipose tissue.In Vitro Cell. Dev. Biol. 25409–418.

    PubMed  Google Scholar 

  82. J. F. Levine and F. E. Stockdale (1984). 3T3-L1 Adipocytes promote the growth of mammary epithelium.Exp. Cell. Res. 151112–122.

    Article  PubMed  Google Scholar 

  83. S. Z. Haslam (1986). Mammary fibroblast influence on normal mouse mammary epithelial cell responses to estrogenin vitro.Cancer Res. 46310–316.

    PubMed  Google Scholar 

  84. F. R. Miller, D. McEachern, and B. E. Miller (1989). Growth regulation of mouse mammary tumor cells in collagen gel cultures by diffusible factors produced by normal mammary gland epithelium and stromal fibroblasts.Cancer Res. 496091–6097.

    PubMed  Google Scholar 

  85. E. F. Howard, D. F. Scott, and C. E. Bennett (1976). Stimulation of thymidine uptake and cell proliferation in mouse embryo fibroblasts by conditioned medium from mammary cells in culture.Cancer Res. 364543–4551.

    PubMed  Google Scholar 

  86. R. S. Talhouk, M. J. Bissell, and Z. Werb (1992). Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution.J. Cell. Biol. 1181271–1282.

    Article  PubMed  Google Scholar 

  87. S. P. Ethier (1996). Human breast cancer cell lines as models of growth regulation and disease progression.J. Mammary Gland Biol. Neoplasia, this issue.

Download references

Author information

Authors and Affiliations

  1. Grace Cancer Drug Center, Roswell Park Cancer Institute, Elm and Carlton Sts., 14263, Buffalo, New York

    Margot M. Ip & Kathleen M. Darcy

Authors
  1. Margot M. Ip
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen M. Darcy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margot M. Ip.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ip, M.M., Darcy, K.M. Three-dimensional mammary primary culture model systems. J Mammary Gland Biol Neoplasia 1, 91–110 (1996). https://doi.org/10.1007/BF02096305

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02096305

Key words

Search

Navigation