Vascular Morphogenesis in the Mammary Gland: Introduction and Overview

  • M. Luisa Iruela-Arispe
  • Maria Asuncion Ortega
  • Sarah Oikemus
  • Michael S. Pepper
Part of the Cardiovascular Molecular Morphogenesis book series (CARDMM)


The mammary gland is unique, it undergoes most of its development well after birth. Although organ immaturity is a constant feature of most tissues after birth, no other structure is associated with the significant changes in size, shape, and function that occur in the breast during puberty, pregnancy, lactation, and involution.


Mammary Gland Mammary Epithelial Cell Mammary Epithelium Normal Mammary Epithelial Cell Vascular Morphogenesis 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bernfield, M., Banerjee, S. D., Koda, J. E., and Rapraeger, A. C. 1984. Remodeling of the basement membrane as a mechanism for morphogenetic tissue interactions. In: Robert, L. Trelstad, ed., The Role of the Extracellular Matrix in Development. Alan, R. Liss, New York, pp. 545–572.Google Scholar
  2. Boudreau, N., Sympson, C. J., Werb, Z., and Bissell, M. J. 1995. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science 267:891–893.PubMedCrossRefGoogle Scholar
  3. Brisken, C., Heineman, A., Chavarria, T., Elenbaas, B., Tan, J., Dey, S. K., McMahon, J. A., McMahon, A. P., and Weinberg, R. A. 2000. Essential function of Wnt-r in mammary gland development downstream of progesterone signaling. Genes Dev. 14:650–654.PubMedGoogle Scholar
  4. Brisken, C., Kaur, S., Chavarria, T., Binart, N., Sutherland, R. L., Weinberg, R. A., Kelly, P. A., and Ormandy, C. J. 1999. Prolactin controls mammary gland development via direct and indirect mechanisms. Dev. Biol. 210:96–106.PubMedCrossRefGoogle Scholar
  5. Brisken, C., Park, S., Vass, T., Lydon, J., O’Malley, B., and Weinberg, R. 1998. A paracrine role for the epithelial progesterone receptor in mammary gland development. Proc. Natl. Acad. Sci. USA 95:5076–5081.PubMedCrossRefGoogle Scholar
  6. Clapp, C., Martial, J. A., Guzman, R. C., Rentier-Delure, F., and Weiner, R. I. 1993. The 16-kilodalton N-terminal fragment of human prolactin is a potent inhibitor of angiogenesis. Endocrinology 133:1292–1299.PubMedCrossRefGoogle Scholar
  7. Clapp, C., and Weiner, R. I. 1992. A specific, high affinity, saturable binding site for the 16kilodalton fragment of prolactin on capillary endothelial cells. Endocrinology 130:1380–1386.PubMedCrossRefGoogle Scholar
  8. Colitti, M., Stefanon, B., and Wilde, C. J. 1999. Apoptotic cell death, bax and bc1–2 expression during sheep mammary gland involution. Anat. Histol. Embryol. 28:257–264.PubMedCrossRefGoogle Scholar
  9. D’Angelo, G., Martini, J. F., Iiri, T., Fantl, W. J., Martial, J., and Weiner, R. I. 1999. 16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells. Mol. Endocrinol. 13:692–704.PubMedCrossRefGoogle Scholar
  10. Daniel, C. W., and Robinson, S. D. 1992. Regulation of mammary growth and function by TGF-beta. Mol. Reprod. Dev. 32:145–151.PubMedCrossRefGoogle Scholar
  11. Daniel, C. W., and Silberstein, G. B. 1987. Postnatal development of the rodent mammary gland. In: Nevile, M. C., and Daniel, C. W., eds. The Mammary Gland: Development, Regulation,and Function. Plenum Press, New York, pp. 3–36.Google Scholar
  12. Danielson, K. G., Oborn, C. J., Durban, E. M., Butel, J. S., and Medina, D 1984. An 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
  13. Duenas, Z., Torner, L., Corbacho, A. M., Ochoa, A., Gutierrez-Ospina, G., Lopez-Barrera, F., Barrios, F. A., Berger, P., Martinez de la Escalera, G., and Clapp, C. 1999. Inhibition of rat cornal angiogenesis by 16-kDa prolactin and by endogenous prolactin-like molecules. Invest. Ophthalmol. Vis. Sci. 40:2498–2505.PubMedGoogle Scholar
  14. Ethier, S. P., and Van de Velde, R. M. 1990. Secretion of a TGF-ß-like growth inhibitor by normal rat mammary epithelial cells in vitro. J. Cell. Physiol. 142:15–20.PubMedCrossRefGoogle Scholar
  15. Farrow, S. N., and Brown, R. 1996. New members of the Bc1–2 family and their protein partners. Curr. Opin. Genet. Dev. 6:45–49.PubMedCrossRefGoogle Scholar
  16. Farrow, S. N., White, J. H. M., Marinou, I., Raven, T., Pun, K. T., Grinham, C. J., Marinou, J. C., and Brown, R. 1995. Cloning of a Bd-2 homolog by interaction with adenovirus Elb 19k. Nature 374:731–733.PubMedCrossRefGoogle Scholar
  17. Faulkin, L. J., Jr., and DeOme, K. B. 1960. Regulation of growth and spacing of gland elements in the mammary fat pad of the C3H mouse. J. Natl. Cancer Inst. 24:953–969.PubMedGoogle Scholar
  18. Feng, Z. W., Marti, A., Jehn, B., Altermatt, H. J., Chicaiza, G., and Jaggi, R. 1995. Glucocorticoid and progesterone inhibit involution and programmed cell-death in the mouse mammary-gland. J. Cell Biol. 131:1095–1103.PubMedCrossRefGoogle Scholar
  19. Furth, P. A. 1999. Introduction: Mammary gland involution and apoptosis of mammary epithelial cells. J. Mammary Gland Biol. Neoplasia 4:123–127.PubMedCrossRefGoogle Scholar
  20. Gibson, L., Holmgreen, S. P., Huang, D. C. S., Bernand, O., Copeland, N. G., Jenkins, N. A., Sutherland, G. R., Baker, E., Adams, J. M., and Cory, S. 1996. Bcl-W, a novel member of the Bc1–2 family, promotes cell-survival. Oncogene 13:665–675.PubMedGoogle Scholar
  21. Green, D., and Kroemer, G. 1998. The central executioners of apoptosis: caspases or mitochondria? Trends Cell Biol. 8:267–271.PubMedCrossRefGoogle Scholar
  22. Gross, A., Jockel, J., Wei, M. C., and Korsmeyer, S. J. 1998. Enforced dimerization of Bax results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J. 17:3878–3885.PubMedCrossRefGoogle Scholar
  23. Gumkowski, F., Kaminska, G., Kaminski, M., Morrissey, L. W., and Auerbach, R. 1987. Heterogeneity of mouse vascular endothelium. In vitro studies of lymphatic, large blood vessel and microvascular endothelial cells. Blood Vessels 24:11–23.Google Scholar
  24. Haslam, S. Z. 1986. Mammary fibroblast influence on normal mouse mammary epithelial cell responses to estrogen in vitro. Cancer Res. 46:310–316.PubMedGoogle Scholar
  25. Haslam, S. Z., and Levely, M. L. 1985. Estradiol responsiveness of normal mouse mammary cells in primary cell culture: association of mammary fibroblasts with estradiol regulation of progesterone receptors. Endocrinology 116:1835–1841.PubMedCrossRefGoogle Scholar
  26. Hewett, P. W., Murray, J. C., Price, E. A., Watts, M. E., and Woodcock, M. 1993. Isolation and characterization of microvessel endothelial cells from human mammary adipose tissue. In Vitro Cell Dey. Biol. Anim. 29A:325–331.CrossRefGoogle Scholar
  27. Howlett, A. R., and Bissell, M. J. 1993. The influence of tissue microenvironment (stroma and extracellular matrix) on the development and function of mammary epithelium. Epithelial Cell Biol. 2(2):79–89.PubMedGoogle Scholar
  28. Humphreys, R., Lydon, J., O’Malley, B., and Rosen, J. 1997. Mammary gland development is mediated by both stromal and epithelial progesterone receptors. Mol. Endocrinol. 11:801–811.PubMedCrossRefGoogle Scholar
  29. Imagawa, W, Tomooka, Y., Hamamoto, S., and Nandi, S. 1985. Stimulation of mammary epithelial cell growth in vitro: interaction of epidermal growth factor and mammogenic hormones. Endocrinology 116:1514–1524.PubMedCrossRefGoogle Scholar
  30. Imagawa, W, Tomooka, Y., and Nandi, S. 1982. Serum-free growth of normal and tumor mouse mammary epithelial cells in primary culture. Proc. Natl. Acad. Sci. USA 79:4074–4077.PubMedCrossRefGoogle Scholar
  31. Iruela-Arispe, M. L., Bornstein, P., Sage, H. 1991. Thrombospondin exerts an antiangiogenic effect on cord formation by endothelial cells in vitro. Proc. Nat. Acad. Sci. USA 88:5026–5030.PubMedCrossRefGoogle Scholar
  32. Iruela-Arispe, M. L., Lombardo, M., Krutzsch, H. C., Lawler, J., and Roberts, D. D. 1999a. Inhibition of angiogenesis by thrombospondin-1 is mediated by 2 independent regions within the type 1 repeats. Circulation 100:1423–1431.CrossRefGoogle Scholar
  33. Iruela-Arispe, M. L., Ortega, M. A., and Vazquez, F. 1999b. Anti-angiogenic domain of thrombospondin. In: Rubany, G., ed. Angiogenesis in Health and Disease: Basic Mechanisms and Clinical Applications. pages:349–357.Google Scholar
  34. Jacobson, M. D. 1997. Apoptosis: Bcl-2-related proteins get connected. Curr. Biol. 7:R277–R281.PubMedCrossRefGoogle Scholar
  35. Jerry, D. J., Pinkas, J., Kuperwasser, C., Dickinson, E. S., and Naber, S. P. 1999. Regulation of p53 and its targets during involution of the mammary gland. J. Mammary Gland Biol. Neoplasia 4:177–181.PubMedCrossRefGoogle Scholar
  36. Jhappan, C., Geiser, A. G., Kordon, E. C., Bagheri, D., Hennighausen, L., Roberts, A. B., Smith, G. H., and Merlino, G. 1993. Targeting expression of a transforming growth factor beta 1 transgene to the pregnant mammary gland inhibits alveolar development and lactation. EMBO J. 12:1835–1845.PubMedGoogle Scholar
  37. Jhappan, C., Stable, C., Harkins, R. N., Fausto, N., Smith, G. H., and Merlino, G. T. 1990. TGFa overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61:1137–1146.PubMedCrossRefGoogle Scholar
  38. Kim-Schulze, S., McGowan, L. A., Hubchak, S. C., Cid, M. C., Martin, M. B., Kleinman, H. K., Greene, G. L., and Schnaper, H. W. 1996. Expression of an estrogen receptor by human coronary artery and umbilical vein endothelial cells. Circulation 94:1402–1407.PubMedCrossRefGoogle Scholar
  39. Knabbe, C., Lippman, M. E., Wakefield, L. M., Flanders, K. C., Kasid, A., Derynck, R., and Dickson, R. B. 1987. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48:417–428.PubMedCrossRefGoogle Scholar
  40. Knight, C. H., and Peaker, M. 1982. Development of the mammary gland./ Reprod. Fertil. 65:521–536.CrossRefGoogle Scholar
  41. Knudson, C. M., and Korsmeyer, S. J. 1997. Bel-2 and Bax function independently to regulate cell death. Nat. Genet. 16:358–363.PubMedCrossRefGoogle Scholar
  42. Kratochwil, K. 1971. In vitro analysis of the hormonal basis for the sexual dimorphism in the embryonic development of the mouse mammary gland. J. Embryol. Exp. Morphol. 25:141–153.PubMedGoogle Scholar
  43. Kratochwil, K. 1987. Epithelium-mesenchyme interactions in the fetal mammary gland. In: Medina, D., Kidwell, W., Heppner, G., and Anderson, E. eds. Cellular and Molecular Biology of Mammary Cancer. Plenum Press, New York, pp. 67–80.CrossRefGoogle Scholar
  44. Lee, H., Struman, I., Clapp, C., Martial, J., and Weiner, R. I. 1998. Inhibition of urokinase activity by the antiangiogenic factor 16K prolactin: activation of plasminogen activator inhibitor 1 expression. Endocrinology 139:3696–3703.PubMedCrossRefGoogle Scholar
  45. Lin, C. Q., and Bissel, M. J. 1993. Multi-faceted regulation of cell differentiation by extra-cellular matrix. FASEB J. 7:737–743.PubMedGoogle Scholar
  46. Lubahn, D. B., Moyer, J. S., Golding, T. S., Couse, J. F., Korach, K. S., and Smithies, O. 1993. Alteration of reproductive function but not prenatal sexual development after insertional disruption of the mouse estrogen receptor gene. Proc. Natl. Acad. Sci. USA 90:11162–11166.PubMedCrossRefGoogle Scholar
  47. Lund, L. R., Romer, J., Thomasset, N., Solberg, H., Pyke, C., Bissell, M. J., Dano, K., and Werb, Z. 1996.2 distinct phases of apoptosis in mammary-gland involution-proteinaseindependent and proteinase-dependent pathways. Development 122:181–193.PubMedGoogle Scholar
  48. Lydon, J. P., DeMayo, F. J., Funk, C. R., Mani, S. K., Hughes, A. R., Montgomery Jr., C. A., Shyamala, G., Conneely, O. M., and O’Malley, B. W. 1995. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 9:2266–2278.PubMedCrossRefGoogle Scholar
  49. Lyons, W. R. 1958. Hormonal synergism in mammary growth. Proc. R. Soc. (Lond.) [B] 49:303–325.CrossRefGoogle Scholar
  50. Matsui, Y., Halter, S. A., Holt, J. T., Hogan, B. L. M., and Coffey, R. J. 1990. Development of mammary hyperplasia and neoplasia in MMTV-TGFa transgenic mice. Cell 61:1147–1155.PubMedCrossRefGoogle Scholar
  51. Matsumoto, M., Kurohmaru, M., Hayashi, Y., Nishinakagawa, H., and Otsuka, J. 1994. Per-meability of mammary gland capillaries to ferritin in mice. J. Vet. Med. Sci. 56:65–70.PubMedCrossRefGoogle Scholar
  52. Matsumoto, M., Nishinakagawa, H., Kurohmaru, M., and Hayashi, Y. 1995a. Effects of estrogen and progesterone on the parenchyma and blood vessels of the mammary gland in ovariectomized adult mice. J. Vet. Med. Sci. 57:39–44.CrossRefGoogle Scholar
  53. Matsumoto, M., Nishinakagawa, H., Kurohmaru, M., Hayashi, Y., and Awal, M. A. 1995b. Ultrastructural changes in fat cells and blood capillaries of the mammary gland in starved mice. J. Vet. Med. Sci. 57:733–736.CrossRefGoogle Scholar
  54. Matsumoto, M., Nishinakagawa, H., Kurohmaru, M., Hayashi, Y., and Otsuka, J. 1992a. Effects of estrogen and progesterone on the development of the mammary gland and the associated blood vessels in ovariectomized mice. J. Vet. Med. Sci. 54:1117–1124.CrossRefGoogle Scholar
  55. Matsumoto, M., Nishinakagawa, H., Kurohmaru, M., Hayashi, Y, and Otsuka, J. 1992b. Pregnancy and lactation affect the microvasculature of the mammary gland in mice. J. Vet. Med. Sci. 54:937–943.CrossRefGoogle Scholar
  56. McGrath, C. M. 1983. Augmentation of the response of normal mammary epithelial cells to estradiol by mammary stroma. Cancer Res. 43:1355–1360.PubMedGoogle Scholar
  57. Metcalfe, A. D., Gilmore, A., Klinowka, T., Oliver, J., Valentijn, A. J., Brown, R., Ross, A., MacGregor, G., Hickman, J. A., and Streuli, C. H. 1999. Developmental regulation of Bd-2 family protein expression in the involuting mammary gland. J. Cell Sci. 112:1771–1783.PubMedGoogle Scholar
  58. Metcalfe, A., and Streuli, C. 1997. Epithelial appoptosis. BioEssays 19:711–720.PubMedCrossRefGoogle Scholar
  59. Morales, D. E., McGowan, K. A., Grant, D. S., Maheshwari, S., Bhartiya, D., Cid, M. C., Kleinman, H. K., and Schnaper, H. W. 1995. Estrogens promote angiogenic activity in human umbilical vein endothelial cells in vitro and in a murine model. Circulation 91:755–763.PubMedCrossRefGoogle Scholar
  60. Nandi, S. 1958. Endocrine control of mammary-gland development and function in the C3H/He Crgl mouse. J. Natl. Cancer Inst. 21:1039–1063.PubMedGoogle Scholar
  61. Nandi, S., Imagawa, W, Tomooka, Y., McGrath, M. F., and Edery, M. 1984. Collagen gel culture system and analysis of estrogen effects on mammary carcinogenesis. Arch. Toxicol. 55:91–96.PubMedCrossRefGoogle Scholar
  62. Oltavai, Z. N., Milliman, C. L., and Korsmeyer, S. J. 1993. Bd-2 heterodimerizes in-vivo with a conserved homolog, Bax, that accelerates programmed cell-death. Cell 74:609–619.CrossRefGoogle Scholar
  63. Ormandy, C. J., Camus, A., Barra, J., Damotte, D., Lucas, B., Buteau, H., Edery, M., Brousse, N., Babinet, C., Binart, N., and Kelly, P. A. 1997. Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev. 11:167–178.PubMedCrossRefGoogle Scholar
  64. Ortega, M. A., and Iruela-Arispe, M. L. 2001. Thrombospondin-1 is an endogenous regulator of angiogenesis in the mammary gland. J. Cell Biol. (submitted).Google Scholar
  65. Pepper, M. S., Baetens, D., Mandriota, S. J., Di Sanza, C., Oikemus, S., Lane, T. F., Soriano, J. V., Montesano, R., and Iruela-Arispe, M. L. 2000. Regulation of VEGF and VEGF receptor expression in the rodent mammary gland during pregnancy, lactation and involution. Dev. Dyn. 218:507–524.PubMedCrossRefGoogle Scholar
  66. Pierce, D. F., Jr., Johnson, M. D., Matsui, Y., Robinson, S. D., Gold, L. I., Purchio, A. F., Daniel, C. W., Hogan, B. L., and Moses, H. L. 1993. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev. 7:2308–2317.PubMedCrossRefGoogle Scholar
  67. Propper, A. 1970. Experimental study of the 1st stages of mammary morphogenesis. Annee Biol. 9:267–275.PubMedGoogle Scholar
  68. Pujuguet, P., Simian, M., Liaw, J., Timpl, R., Werb, Z., and Bissell, M. J. 2000. Nidogen-1 regulates laminin-l-dependent mammary-specific gene expression. J. Cell Sci. 113:849–858.PubMedGoogle Scholar
  69. Robinson, G. W., and Hennighausen, L. 1997. Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Development 124:2701–2708.PubMedGoogle Scholar
  70. Rubanyi, G. M., Freay, A. D., Kauser, K., Sukovich, D., Burton, G., Lubahn, D. B., Couse, J. F., Curtis, S. W., and Korach, K. S. 1997. Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. J. Clin. Invest. 99:2429–2437.PubMedCrossRefGoogle Scholar
  71. Sakakura, T. 1987. Mammary embryogenesis. In: Neville, M. C., and Daniel, C. W., eds. The Mammary Gland: Development,Regulation, and Function. Plenum Press, New York, pp. 37–66.Google Scholar
  72. Sakakura, T. 1991. New aspects of stroma-parenchyma relations in mammary gland differentiation. Int. Rev. Cytol. 125:165–202.PubMedCrossRefGoogle Scholar
  73. Sakakura, T., Sakagami, Y., and Nishizuka, Y. 1982. Dual origin of mesenchymal tissues participating in mouse mammary gland embryogenesis. Dev. Biol. 91:202–207.PubMedCrossRefGoogle Scholar
  74. Sandgren, E. P., Luetteke, N. C., Palmiter, R. D., Brinster, R. L., and Lee, D. C. 1990. Over-expression of TGFa in transgenic mice: Induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell 61:1121–1135.PubMedCrossRefGoogle Scholar
  75. Shekhar, M. P., Werdell, J., and Tait, L. 2000. Interaction with endothelial cells is a prerequisite for branching ductal-alveolar morphogenesis and hyperplasia of preneoplastic human breast epithelial cells: regulation by estrogen. Cancer Res. 60:439–449.PubMedGoogle Scholar
  76. Silberstein, G. B., and Daniel, C. W. 1987. Reversible inhibition of mammary gland growth by transforming growth factor-beta. Science 237:291–293.PubMedCrossRefGoogle Scholar
  77. Soemarwoto, I. N., and Bern, H. A. 1958. The effects of hormones on the vascular pattern of the mouse mammary gland. Am. J. Anat. 103:403–435.PubMedCrossRefGoogle Scholar
  78. Spyridopoulos, I., Sullivan, A. B., Kearney, M., Isner, J. M., and Losordo, D. W. 1997. Estrogen receptor-mediated inhibition of human endothelial cell apoptosis: estradiol as a survival factor. Circulation 95:1505–1514.PubMedCrossRefGoogle Scholar
  79. Sternlicht, M. D., Lochter, A., Sympson, C. J., Huey, B., Rougier, J., Gray, J. W., Finkel, D., Bissell, M. J., and Werb, Z. 1999. The stromal proteinase MMP3/stromelysin-1 promotes mammary carcinogenesis. Cell 98:137–146.PubMedCrossRefGoogle Scholar
  80. Strange, R., Li, F., Saurer, S., Burkhardt, A., and Friis, R. R. 1992. Apoptotic cell-death and tissue remodeling during mouse mammary-gland involution. Development 115:49–58.PubMedGoogle Scholar
  81. Streuli, C. H., Dive, C., Hickman, J. A., Farrelly, N., and Metcalfe, A. 1997. Control of apoptosis in breast epithelium. Endocr. Rel. Cancer 4:45–53.CrossRefGoogle Scholar
  82. Sudhakaran, P. R., Ambili, M., and Philip, S. 1999. Matrix metalloproteinase in mammary gland remodeling-modulation by glycosaminoglycans. Biosci. Rep. 19:485–490.PubMedCrossRefGoogle Scholar
  83. Sympson, C. J., Talhouk, R. S., Alexander, C. M., Chin, J. R., Clift, S. M., Bissell, M. J., and Werb, Z. 1994. Targeted expression of stromelysin-1 in mammary gland provides evidence for a role of proteinases in branching morphogenesis and the requirement for an intact basement membrane for tissue-specific gene expression. J. Cell Biol. 125:681–693.PubMedCrossRefGoogle Scholar
  84. Thurston, G., Murphy, T., Baluk, P., Lindsey, J., and McDonald, D. 1998. Angiogenesis in mice with chronic airway inflammation: strain-dependent differences. Am. J. Pathol. 153:1099–1112.PubMedCrossRefGoogle Scholar
  85. Tolsma, S. S., Volpert, O. V., Good, D. J., Frazier, W. A., Polverini, P. J., and Bouck, N. 1993. Peptides derived from 2 separate domains of the matrix protein thrombospondin1 have anti-angiogenic activity. J. Cell Biol. 122:497–511.PubMedCrossRefGoogle Scholar
  86. Tonner, E., Barber, M. C., Travers, M. T., Logan, A., and Flint, D. J. 1997. Hormonal control of insulin-like growth factor binding protein-5 production in the involuting mammary gland of the rat. Endocrinology 138:5101–5107.PubMedCrossRefGoogle Scholar
  87. Turner, C. W., and Gomez, E. T. 1933. The normal development of the mammary gland of the male and female albino mouse. I. Intrauterine. Mo. Agric. Exp. Stn. Res. Bull. 182:3–20.Google Scholar
  88. Vazquez, F., Rodriguez-Manzaneque, J. C., Lydon, J. P., Edwards, D. P., O’Malley, B. W., and Iruela-Arispe, M. L. 1999. Progesterone regulates proliferation of endothelial cells. J. Biol. Chem. 274:2185–2192.PubMedCrossRefGoogle Scholar
  89. Wahl, H. M. 1915. Development of the blood vessels of the mammary gland in the rabbit. Am. J. Anat. 18:515–524.CrossRefGoogle Scholar
  90. Wiesen, J. F., Young, P., Werb, Z., and Cunha, G. R. 1999. Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development 126:335–344.PubMedGoogle Scholar
  91. Williams, J. M., and Daniel, C. W. 1983. Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev. Biol. 97:274–290.PubMedCrossRefGoogle Scholar
  92. Yang, J., Guzman, R., Richards, J., Imagawa, W., McCormack, K., and Nandi, S. 1986. Growth factor-and cyclic nucleotide-induced proliferation of normal and malignant mammary epithelial cells in primary culture. Endocrinology 107:35–41.CrossRefGoogle Scholar
  93. Yang, J., Richards, J., Guzman, R., Imagawa, W., and Nandi, S. 1980a. Sustained growth in primary culture of normal mammary epithelial cells embedded in collagen gels. Proc. Natl. Acad. Sci. USA 77:2088–2092.CrossRefGoogle Scholar
  94. Yasugi, T., Kaido, T., and Uehara, Y. 1989. Changes in density and architecture of microvessels of the rat mammary gland during pregnancy and lactation. Arch. Histol. Cytol. 52:115–122.PubMedCrossRefGoogle Scholar
  95. Zangani, D., Darcy, K. M., Masso-Welch, P. A., Bellamy, E. S., Desole, M. S., and Ip, M. M. 1999a. Multiple differentiation pathways of rat mammary stromal cells in vitro: acquisition of a fibroblast, adipocyte or endothelial phenotype is dependent on hormonal and extracellular matrix stimulation. Differentiation 64:91–101.CrossRefGoogle Scholar
  96. Zangani, D., Darcy, K. M., Shoemaker, S., and Ip, M. M. 1999b. Adipocyte-epithelial interactions regulate the in vitro development of normal mammary epithelial cells. Exp. Cell Res. 247:399–409.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • M. Luisa Iruela-Arispe
  • Maria Asuncion Ortega
  • Sarah Oikemus
  • Michael S. Pepper

There are no affiliations available

Personalised recommendations