Anatomy and Physiology of the Breast

  • Martha C. Johnson

Abstract

This chapter is a review of the development, structure and function of the normal human breast. It is meant to serve as a backdrop and reference for the chapters that follow on pathologies and treatment. It presents an overview of normal gross anatomy, histology, and hormonal regulation of the breast followed by a discussion of its structural and functional changes from embryonic development through postmenopausal involution. This section includes recent data on some of the hormones, receptors, growth factors, transcription factors and genes that regulate this amazing nutritive organ.

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References

  1. 1.
    Romer AS (1970) The vertebrate body., 4th edn. WB Saunders, PhiladelphiaGoogle Scholar
  2. 2.
    Swaminathan N. Strange but true: males can lactate. ScientificAmerican.com. 2007Google Scholar
  3. 3.
    Wuringer E et al (1998) Nerve and vessel supplying ligamentous suspension of the mammary gland. Plast Reconstr Surg. 101(6):1486–93PubMedGoogle Scholar
  4. 4.
    Stranding S (ed). Gray’s anatomy: the anatomical basis of clinical practice. 39th ed. Edinburgh: Elsevier, Churchill, Livingstone; 2005. p. 7Google Scholar
  5. 5.
    Moore KL. Clinically oriented anatomy. 5th ed. Baltimore: Lipincott Williams and Wilkins; 2006Google Scholar
  6. 6.
    Sarhadi NS, Shaw-Dunn J, Soutar DS (1997) Nerve supply of the breast with special reference to the nipple and areola: Sir Astley Cooper revisited. Clin Anat. 10(4):283–8PubMedGoogle Scholar
  7. 7.
    Schlenz I et al (2000) The sensitivity of the nipple-areola complex: an anatomic study. Plast Reconstr Surg. 105(3):905–9PubMedGoogle Scholar
  8. 8.
    Jaspars JJ et al (1997) The cutaneous innervation of the female breast and nipple-areola complex: implications for surgery. Br J Plast Surg. 50(4):249–59PubMedGoogle Scholar
  9. 9.
    Schlenz I, et al Alteration of nipple and areola sensitivity by reduction mammaplasty: a prospective comparison of five techniques. Plast Reconstr Surg. 2005;115(3):743–51; discussion 752–4PubMedGoogle Scholar
  10. 10.
    Wakerley JB. Milk ejection and its control. In: Neill JD, editor. Knobil and Neill’s physiology. San Diego: Elsevier; 2006. p. 3129–3190Google Scholar
  11. 11.
    DelVecchyo C et al (2004) Evaluation of breast sensibility using dermatomal somatosensory evoked potentials. Plast Reconstr Surg. 113(7):1975–83PubMedGoogle Scholar
  12. 12.
    Godwin Y et al (2004) Investigation into the possible cause of subjective decreased sensory perception in the nippleareola complex of women with macromastia. Plast Reconstr Surg. 113(6):1598–606PubMedGoogle Scholar
  13. 13.
    Bloom W, Don Fawcett W. A textbook of histology. 10th ed. Philadelphia: WB Saunders; 1975Google Scholar
  14. 14.
    Franke-Radowiecka A, Wasowicz K (2002) Adrenergic and cholinergic innervation of the mammary gland in the pig. Anat Histol Embryol. 31(1):3–7PubMedGoogle Scholar
  15. 15.
    Papay FA et al (1997) Complex regional pain syndrome of the breast in a patient after breast reduction. Ann Plast Surg. 39(4):347–52PubMedGoogle Scholar
  16. 16.
    Eriksson M et al (1996) Distribution and origin of peptide-containing nerve fibres in the rat and human mammary gland. Neuroscience. 70(1):227–45PubMedGoogle Scholar
  17. 17.
    Ricbourg B (1992) Applied anatomy of the breast: blood supply and innervation. Ann Chir Plast Esthet. 37(6):603–20PubMedGoogle Scholar
  18. 18.
    Naccarato AG et al (2003) Definition of the microvascular pattern of the normal human adult mammary gland. J Anat. 203(6):599–603PubMedGoogle Scholar
  19. 19.
    Weinstein SP, et al Hormonal variations in the vascularity of breast tissue. J Ultrasound Med. 2005;24(1):67–72; quiz 74PubMedGoogle Scholar
  20. 20.
    O’Rahilly M. Carpenter and Swenson, vessels, lymphatic drainage and the breast. 2004Google Scholar
  21. 21.
    Nathanson SD et al (2001) Pathways of lymphatic drainage from the breast. Ann Surg Oncol. 8(10):837–43PubMedGoogle Scholar
  22. 22.
    Braithwaite LR (1923) The flow of lymph from the ileocaecal angel, and its possible bearing on the cause of duodenal and gastric ulcer. Br J Surg. 11:7–26Google Scholar
  23. 23.
    Krag D et al (1998) The sentinel node in breast cancer—a multicenter validation study. N Engl J Med. 339(14):941–6PubMedGoogle Scholar
  24. 24.
    Estourgie SH et al (2004) Lymphatic drainage patterns from the breast. Ann Surg. 239(2):232–7PubMedGoogle Scholar
  25. 25.
    Vendrell-Torne E, Setoain-Quinquer J, Domenech-Torne FM (1971) Study of normal mammary lymphatic drainage using radioactive isotopes. J Nuclear Med. 13(11):801–5Google Scholar
  26. 26.
    Suami H et al (2008) The lymphatic anatomy of the breast and its implications for sentinel lymph node biopsy: a human cadaver study. Ann Surg Oncol. 15(3):863–71PubMedGoogle Scholar
  27. 27.
    Krynyckyi BR, Shim J, Kim CK. Internal mammary chain drainage of breast cancer. Ann Surg. 2004;240(3):557; author reply 558PubMedGoogle Scholar
  28. 28.
    Kellokumpu-Lehtinen P, Johansson RM, Pelliniemi LJ (1987) Ultrastructure of human fetal mammary gland. Anat Rec. 218(1):66–72PubMedGoogle Scholar
  29. 29.
    Herman-Giddens ME et al (1997) Secondary sexual characteristics and menses in young girls seen in office practice: a study from the pediatric research in office settings network. Pediatrics. 99(4):505–12PubMedGoogle Scholar
  30. 30.
    Tanner J (1962) Growth at adolescence., 2nd edn, Blackwell Scientific, OxfordGoogle Scholar
  31. 31.
    Tavassoli FA (1999) Pathology of the breast., 2nd edn. Appleton and Lange, Stamford, CTGoogle Scholar
  32. 32.
    Hussain Z et al (1999) Estimation of breast volume and its variation during the menstrual cycle using MRI and stereology. Br J Radiol. 72(855):236–45PubMedGoogle Scholar
  33. 33.
    Howard BA, Gusterson BA (2000) Human breast development. J Mammary Gland Biol Neoplasia. 5(2):119–37PubMedGoogle Scholar
  34. 34.
    Nelson CM, Bissell MJ (2005) Modeling dynamic reciprocity: engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation. Semin Cancer Biol. 15(5):342–52PubMedGoogle Scholar
  35. 35.
    Rosen PR. Rosen’s breast pathoogy. 2nd ed. Philadelphia, PA: Lippincott williams and Wilkins; 2001Google Scholar
  36. 36.
    Pitelka DR (1988) The mammary gland. In: Weiss L ed) Cell and tissue biology: a textbook of histology. Elsevier Biomedical, New York, pp 880–98Google Scholar
  37. 37.
    Pathology, U.o.V.D.O.I. Gross Anatomy and Histology. 1998-2007 [cited; Available from: www.med-ed.virginia. edu/courses/path/gyn/breast1.cfmGoogle Scholar
  38. 38.
    Cardiff RD (1998) Are the TDLU of the human the same as the LA of mice? J Mammary Gland Biol Neoplasia. 3(1):3–5PubMedGoogle Scholar
  39. 39.
    Moffat DF, Going JJ (1996) Three-dimensional anatomy of complete duct systems in human breast: pathological and developmental implications. J Clin Pathol. 49(1):48–52PubMedGoogle Scholar
  40. 40.
    Ohtake T et al (2001) Computer-assisted complete three-dimensional reconstruction of the mammary ductal/lobular systems: implications of ductal anastomoses for breast-conserving surgery. Cancer. 9(12):2263–72Google Scholar
  41. 41.
    Junqueira L, Carneiro J. Basic histology text and atlas. 10th ed. New York: Lange Medical Books McGraw-Hill; 2003Google Scholar
  42. 42.
    Ferguson DJ (1985) Intraepithelial lymphocytes and macrophages in the normal breast. Virchows Arch A Pathol Anat Histopathol. 407(4):369–78PubMedGoogle Scholar
  43. 43.
    Ross M, Pawlina W. Histology, a text and atlas. 5th ed. Baltimore: Lippincott Williams and Wilkins; 2006Google Scholar
  44. 44.
    Daniel CW, Strickland P, Friedmann Y (1995) Expression and functional role of E-and P-cadherins in mouse mammary ductal morphogenesis and growth. Dev Biol. 169(2):511–9PubMedGoogle Scholar
  45. 45.
    Woodward WA et al (2005) On mammary stem cells. J Cell Sci. 118(Pt 16):3585–94PubMedGoogle Scholar
  46. 46.
    Deugnier MA et al (2002) The importance of being a myoepithelial cell. Breast Cancer Res. 4(6):224–30PubMedGoogle Scholar
  47. 47.
    Monaghan P, Moss D (1996) Connexin expression and gap junctions in the mammary gland. Cell Biol Int. 20(2):121–5PubMedGoogle Scholar
  48. 48.
    Glukhova M et al (1995) Adhesion systems in normal breast and in invasive breast carcinoma. Am J Pathol. 146(3): 706–16PubMedGoogle Scholar
  49. 49.
    Gudjonsson T et al (2002) Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 115(Pt 1):39–50PubMedGoogle Scholar
  50. 50.
    Schmeichel KL, Weaver VM, Bissell MJ (1998) Structural cues from the tissue microenvironment are essential determinants of the human mammary epithelial cell phenotype. J Mammary Gland Biol Neoplasia. 3(2):201–13PubMedGoogle Scholar
  51. 51.
    Radice GL et al (1997) Precocious mammary gland development in P-cadherin-deficient mice. J Cell Biol. 139(4):1025–32PubMedGoogle Scholar
  52. 52.
    Faraldo MM et al (2005) Myoepithelial cells in the control of mammary development and tumorigenesis: data from genetically modified mice. J Mammary Gland Biol Neoplasia. 10(3):211–9PubMedGoogle Scholar
  53. 53.
    Adriance MC et al (2005) Myoepithelial cells: good fences make good neighbors. Breast Cancer Res. 7(5):190–7PubMedGoogle Scholar
  54. 54.
    El-Sabban ME, Abi-Mosleh LF, Talhouk RS (2003) Developmental regulation of gap junctions and their role in mammary epithelial cell differentiation. J Mammary Gland Biol Neoplasia. 8(4):463–73PubMedGoogle Scholar
  55. 55.
    Gudjonsson T et al (2005) Myoepithelial cells: their origin and function in breast morphogenesis and neoplasia. J Mammary Gland Biol Neoplasia. 10(3):261–72PubMedGoogle Scholar
  56. 56.
    Lakhani SR, O’Hare MJ (2001) The mammary myoepithelial cell—Cinderella or ugly sister? Breast Cancer Res. 3(1):1–4PubMedGoogle Scholar
  57. 57.
    Liu S et al (2006) Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 66(12):6063–71PubMedGoogle Scholar
  58. 58.
    Hennighausen L, Robinson GW (2005) Information networks in the mammary gland. Nat Rev Mol Cell Biol. 6(9):715–25PubMedGoogle Scholar
  59. 59.
    Savarese TM et al (2006) Normal breast stem cells, malignant breast stem cells, and the perinatal origin of breast cancer. Stem Cell Rev. 2(2):103–10PubMedGoogle Scholar
  60. 60.
    Smalley M, Ashworth A (2003) Stem cells and breast cancer: a field in transit. Nat Rev Cancer. 3(11):832–44PubMedGoogle Scholar
  61. 61.
    Chepko G, Smith GH (1997) Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell. 29(2):239–53PubMedGoogle Scholar
  62. 62.
    Smith GH, Medina D (1988) A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland. J Cell Sci. 90(Pt 1):173–83PubMedGoogle Scholar
  63. 63.
    Smith GH, Strickland P, Daniel CW (2002) Putative epithelial stem cell loss corresponds with mammary growth senescence. Cell Tissue Res. 310(3):313–20PubMedGoogle Scholar
  64. 64.
    Daniel CW et al (1968) The in vivo life span of normal and preneoplastic mouse mammary glands: a serial transplantation study. Proc Natl Acad Sci USA. 61(1):53–60PubMedGoogle Scholar
  65. 65.
    Kordon EC, Smith GH (1998) An entire functional mammary gland may comprise the progeny from a single cell. Development. 125(10):1921–30PubMedGoogle Scholar
  66. 66.
    Shackleton M et al (2006) Generation of a functional mammary gland from a single stem cell. Nature. 439(7072):84–8PubMedGoogle Scholar
  67. 67.
    Stingl J et al (1998) Phenotypic and functional characterization in vitro of a multipotent epithelial cell present in the normal adult human breast. Differentiation. 63(4):201–13PubMedGoogle Scholar
  68. 68.
    Villadsen R et al (2007) Evidence for a stem cell hierarchy in the adult human breast. J Cell Biol. 177(1):87–101PubMedGoogle Scholar
  69. 69.
    Welm BE et al (2002) Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol. 245(1):42–56PubMedGoogle Scholar
  70. 70.
    Clarke RB (2005) Isolation and characterization of human mammary stem cells. Cell Prolif. 38(6):375–86PubMedGoogle Scholar
  71. 71.
    Matulka LA, Triplett AA, Wagner KU (2007) Parity-induced mammary epithelial cells are multipotent and express cell surface markers associated with stem cells. Dev Biol. 303(1):29–44PubMedGoogle Scholar
  72. 72.
    Russo J et al (2006) The concept of stem cell in the mammary gland and its implication in morphogenesis, cancer and prevention. Front Biosci. 11:151–72PubMedGoogle Scholar
  73. 73.
    Stingl J et al (2005) Epithelial progenitors in the normal human mammary gland. J Mammary Gland Biol Neoplasia. 10(1):49–59PubMedGoogle Scholar
  74. 74.
    Wagner KU, Smith GH (2005) Pregnancy and stem cell behavior. J Mammary Gland Biol Neoplasia. 10(1):25–36PubMedGoogle Scholar
  75. 75.
    Dontu G et al (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17(10):1253–70PubMedGoogle Scholar
  76. 76.
    Liu S, Dontu G, Wicha MS (2005) Mammary stem cells, self-renewal pathways, and carcinogenesis. Breast Cancer Res. 7(3):86–95PubMedGoogle Scholar
  77. 77.
    Guelstein VI et al (1993) Myoepithelial and basement membrane antigens in benign and malignant human breast tumors. Int J Cancer. 53(2):269–77PubMedGoogle Scholar
  78. 78.
    Prince JM et al (2002) Cell-matrix interactions during development and apoptosis of the mouse mammary gland in vivo. Dev Dyn. 223(4):497–516PubMedGoogle Scholar
  79. 79.
    Woodward TL et al (2001) Fibronectin and the alpha(5) beta(1) integrin are under developmenal and ovarian steroid regulation in the normal mouse mammary gland. Endicrinology. 142(7):3214–22Google Scholar
  80. 80.
    Streuli CH, Bissell MJ (1990) Expression of extracellular matrix components is regulated by substratum. J Cell Biol. 110(4):1405–15PubMedGoogle Scholar
  81. 81.
    Pullan S et al (1996) Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium. J Cell Sci. 109(Pt 3):631–42PubMedGoogle Scholar
  82. 82.
    Streuli C (1999) Extracellular matrix remodelling and cellular differentiation. Curr Opin Cell Biol. 11(5):634–40PubMedGoogle Scholar
  83. 83.
    Novaro V, Roskelley CD, Bissell MJ (2003) Collagen-IV and laminin-1 regulate estrogen receptor alpha expression and function in mouse mammary epithelial cells. J Cell Sci. 116(Pt 14):2975–86PubMedGoogle Scholar
  84. 84.
    Weir ML et al (2006) Dystroglycan loss disrupts polarity and beta-casein induction in mammary epithelial cells by perturbing laminin anchoring. J Cell Sci. 119(Pt 19):4047–58PubMedGoogle Scholar
  85. 85.
    Streuli CH et al (1995) Laminin mediates tissue-specific gene expression in mammary epithelia. J Cell Biol. 129(3):591–603PubMedGoogle Scholar
  86. 86.
    Farrelly N et al (1999) Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling. J Cell Biol. 144(6):1337–48PubMedGoogle Scholar
  87. 87.
    Pujuguet P et al (2000) Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression. J Cell Sci. 113(Pt 5):849–58PubMedGoogle Scholar
  88. 88.
    Streuli CH, Edwards GM (1998) Control of normal mammary epithelial phenotype by integrins. J Mammary Gland Biol Neoplasia. 3(2):151–63PubMedGoogle Scholar
  89. 89.
    Li N et al (2005) Betal integrins regulate mammary gland proliferation and maintain the integrity of mammary alveoli. Embo J. 24(11):1942–53PubMedGoogle Scholar
  90. 90.
    Klinowska TC et al (1989) Laminin and betal integrins are crucial for normal mammary gland development in the mouse. Dev Biol. 215(1):13–32Google Scholar
  91. 91.
    Barcellos-Hoff MH et al (1989) Functional differentiation and alveolar morphogenesis of primary mammary cultures on reconstituted basement membrane. Development. 105(2):223–35PubMedGoogle Scholar
  92. 92.
    Blatchford DR et al (1999) Influence of microenvironment on mammary epithelial cell survival in primary culture. J Cell Physiol. 18(2):304–11Google Scholar
  93. 93.
    Neville MC (2006) Lactation and its hormonal control. In: Neill JD (ed.) Knobil and Neill’s Physiology of Reproduction. San Diego: Elsevier. p. 2993–3054Google Scholar
  94. 94.
    Eyden BP et al (1986) Intralobular stromal fibroblasts in the resting human mammary gland: ultrastructural properties and intercellular relationships. J Submicrosc Cytol. 18(2):397–408PubMedGoogle Scholar
  95. 95.
    Atherton AJ et al (1992) Dipeptidyl peptidase IV expression identifies a functional sub-population of breast fibroblasts. Int J Cancer. 50(1):15–9PubMedGoogle Scholar
  96. 96.
    Sadlonova A et al (2005) Breast fibroblasts modulate epithelial cell proliferation in three-dimensional in vitro coculture. Breast Cancer Res. 7(1):R46–59PubMedGoogle Scholar
  97. 97.
    Parmar H, Cunha GR (2004) Epithelial-stromal interactions in the mouse and human mammary gland in vivo. Endocr Relat Cancer. 11(3):437–58PubMedGoogle Scholar
  98. 98.
    Boyd NF et al (2006) Mammographic density: a homonally responsive risk factor for breast cancer. J Br Menopause Soc. 12(4):186–93PubMedGoogle Scholar
  99. 99.
    Gouon-Evans V, Lin EY, Pollard JW (2002) Requirement of macrophages and eosonophils and their cytokines/chemokines for mammary gand development. Breast Cancer Res. 4(4):155–64PubMedGoogle Scholar
  100. 100.
    Schwertfeger KL, Rosen JM, Cohen DA (2006) Mammary gland macrophages: pleiotropic functions in mammary development. J Mammary Gland Biol Neoplasia. 11(3–4):229–38PubMedGoogle Scholar
  101. 101.
    Monke J et al (2002) Do inflammatory cells participate in mammary gland involution? J Mammary Gland Biol Neoplasia. 7(2):163–76Google Scholar
  102. 102.
    Sternlicht MD (2006) Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis. Breast Cancer Res. 8(1):201PubMedGoogle Scholar
  103. 103.
    Nishimura T (2003) Expression of potential lymphocyte trafficking mediator molecules in the mammary gland. Vet Res. 34(1):3–10PubMedGoogle Scholar
  104. 104.
    Dabiri S et al (2004) The presence of stromal mast cells identifies a subset of invasive breast cancers with a favorable prognosis. Mod Pathol. 17(6):690–5PubMedGoogle Scholar
  105. 105.
    Hartveit F (1993) Mast cell association with collagen fibres in human breast stroma. Eur J Morphol 31(3)209–18PubMedGoogle Scholar
  106. 106.
    Popescu LM, Andrei F, Hinescu ME (2005) Snapshots of mammary gland interstitial cells: mythelene-blue vital staining and c-kit immunopositivity. J Cell Mol Med. 9(2):476–7PubMedGoogle Scholar
  107. 107.
    Popescu LM et al (2005) The connective connection: interstitial cells of Cajal (ICC) and ICC-like cells establish synapses with immunoreactive cells. Electron microscope study in situ. J Cell Mol Med. 9(3):714–30PubMedGoogle Scholar
  108. 108.
    Radu E et al (2005) Cajal-type cells from human mammary gland stroma: phenotype characteristics in cell culture. J Cell Mol Med. 9(3):748–52PubMedGoogle Scholar
  109. 109.
    Gherghiceanu M, Popescu LM (2005) Interstitial Cajal-like cells (ICLC) in human resting mammary gland stroma. Transmission electron microscope (TEM) identification. J Cell Mol Med. 9(4):893–910PubMedGoogle Scholar
  110. 110.
    Haslam SZ, Woodward TL (2003) Host microenvironment in breast cancer development: epithelial-cell-stromal-cell interactions and steroid hormone action in normal and cancerous mammary gland. Breast Cancer Res. 5(4):208–15PubMedGoogle Scholar
  111. 111.
    Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell. 110(6):673–87PubMedGoogle Scholar
  112. 112.
    Schatzmann F, Mardow R, Streuli CH (2003) Integrin signaling and mammary cell function. J Mammary Gland Biol Neoplasia. 8(4):395–408PubMedGoogle Scholar
  113. 113.
    Alowami S et al (2003) Mammographic density is related to stroma and stromal proteoglycan expression. Breast Cancer Res. 5(5):R129–35PubMedGoogle Scholar
  114. 114.
    Delehedde M et al (2001) Proteoglycans: pericellular and cell surface multireceptors that integrate external stimuli in the mammary gland. J Mammary Gland Biol Neoplasia. 6(3):253–73PubMedGoogle Scholar
  115. 115.
    Silverman AJ, Livne I, Witkin JW (1994) The gonadotropin-releasing hormone (GnRH), neuronal systems: immunocytochemistry and in situ hybridization. In: Knobil E, Neill JD (eds) The Physiology of Reproduction. Raven, New York, pp. 1683–709Google Scholar
  116. 116.
    Arthur Guyton C, John Hall E. Textbook of medical physiology. 11th ed. Elsevier Saunders. p. 1018Google Scholar
  117. 117.
    Seagroves TN et al (2003) HIF1alpha is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland. Development, 130(8):1713–24PubMedGoogle Scholar
  118. 118.
    Speirs V et al (2002) Distinct expression patterns of ER alpha and ER beta in normal human mammary gland. J Clin Pathol. 55(5):371–4PubMedGoogle Scholar
  119. 119.
    Levin ER (2005) Integration of the extranuclear and nuclear actions of estrogen. Mol Endocrinol 19(8)):1951–9PubMedGoogle Scholar
  120. 120.
    Li X et al (2004) Single-chain estrogen receptors (ERs) reveal that the ERalpha/beta heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways. Mol Cell Biol. 24(17):7681–94PubMedGoogle Scholar
  121. 121.
    Clarke RB et al (1997) Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res. 57(22):4987–91PubMedGoogle Scholar
  122. 122.
    Howell A (2006) Pure oestrogen antagonists for the treatment of advanced breast cancer. Endocr Relat Cancer 13(3):689–706PubMedGoogle Scholar
  123. 123.
    Hall JM, McDonnell DP (1999) The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology. 140(12):5566–78PubMedGoogle Scholar
  124. 124.
    Asselin-Labat ML et al (2006) Steroid hormone receptor status of mouse mammary stem cells. J Natl Cancer Inst. 98(14):1011–4PubMedGoogle Scholar
  125. 125.
    Asselin-Labat ML et al (2007) Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differetiation. Nat Cell Biol. 9(2):201–9PubMedGoogle Scholar
  126. 126.
    Sleeman KE et al (2007) Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol. 176(1):19–26PubMedGoogle Scholar
  127. 127.
    Clarke RB (2006) Ovarian steroids and the human breast: regulation of stem cells and cell proliferation. Maturitas. 54(4):327–34PubMedGoogle Scholar
  128. 128.
    Cheng G et al (2004) Estrogen receptors ER alpha and ER beta in proliferation in the rodent mammary gland. Proc Natl Acad Sci USA. 101(11):3739–46PubMedGoogle Scholar
  129. 129.
    Khan SA, Bhandare D, Chatterton RT Jr (2005) The local hormonal environment and related biomarkers in the normal breast. Endocr Relat Cancer. 12(3):497–510PubMedGoogle Scholar
  130. 130.
    Mallepell S et al (2006) Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci USA. 103(7):2196–201PubMedGoogle Scholar
  131. 131.
    Forster C et al (2002) Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci USA. 99(24):15578–83PubMedGoogle Scholar
  132. 132.
    Seagroves TN, Rosen JM. Control of mammary epithelial cell proliferation: the unique role of the progesterone receptor. In: Burnstein K, editor. Sex hormones and cell cycle regulation. Kluwer; 2002. p. 33–55Google Scholar
  133. 133.
    Conneely OM, Jericevic BM, Lydon JP (2003) Progesterone receptors in mammary gland development and tumorigenesis. J Mammary Gland Biol Neoplasia. 8(2):205–14PubMedGoogle Scholar
  134. 134.
    Leonhardt SA, Boonyaratanakornkit V, Edwards DP (2003) Progesterone receptor transcription and non-transcription signaling mechanisms. Steroids. 68(10–13):761–70PubMedGoogle Scholar
  135. 135.
    Aupperlee MD, Haslam SZ (2007) Differential hormonal regulation and function of progesterone receptor isoforms in normal adult mouse mammary gland. Endocrinology. 148(5):2290–300PubMedGoogle Scholar
  136. 136.
    Lydon JP, Sivaraman L, Conneely OM (2000) A reappraisal of progesterone action in the mammary gland. J Mammary Gland Biol Neoplasia. 5(3):325–38PubMedGoogle Scholar
  137. 137.
    Cunha GR et al (1997) Elucidation of a role for stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J Mammary Gland Biol Neoplasia. 2(4):393–402PubMedGoogle Scholar
  138. 138.
    Brisken C, Rajaram RD (2006) Alveolar and lactogenic differentiation. J Mammary Gland Biol Neoplasia. 11(3–4):239–48PubMedGoogle Scholar
  139. 139.
    Yang Y et al (1995) Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland. J Cell Biol. 131(1):215–26PubMedGoogle Scholar
  140. 140.
    Kariagina A, Aupperlee MD, Haslam SZ (2007) Progesterone receptor isoforms and proliferation in the rat mammary gland during development. Endocrinology. 148(6):2723–36PubMedGoogle Scholar
  141. 141.
    Eigeliene N, Harkonen P, Erkkola R (2006) Effects of estradiol and medroxyprogesterone acetate on morphology, proliferation and apoptosis of human breast tissue in organ cultures. BMC Cancer. 6:246PubMedGoogle Scholar
  142. 142.
    Freeman ME et al (2000) Profactin: structure, function and regulation of secretion. Physiol Rev. 80(4):1523–631PubMedGoogle Scholar
  143. 143.
    Horseman ND (1999) Prolactin and mammary gland development. J Mammary Gland Biol Neoplasia. 4(1):79–88PubMedGoogle Scholar
  144. 144.
    Dong J. Tsai-Morris CH, Dufau ML (2006) A novel estradiol/estrogen receptor alpha-dependent transcriptional mechanism controls expression of the human prolactin receptor. J Biol Chem. 281(27):18825–36PubMedGoogle Scholar
  145. 145.
    Honda K et al (2004) Prolactin releasing peptides modulate background firing rate and milk-ejection related burst of oxytocin cells in the supraoptic nucleus. Brain Res Bull. 63:315–9PubMedGoogle Scholar
  146. 146.
    Bussolati G et al (1996) Immunolocalization and gene expression of oxytocin receptors in carcinomas and non-neoplastic tissues of the breast. Am J Pathol. 148(6):1895–903PubMedGoogle Scholar
  147. 147.
    Reversi A, Cassoni P, Chini B (2005) Oxytocin receptor signaling in myoepithelial and cancer cells. J Mammary Gland Biol Neoplasia. 10(3):221–9PubMedGoogle Scholar
  148. 148.
    Kleinberg DL, Feldman M, Ruan W (2000) IGF-I: an essentical factor in terminal end bud formation and duc tal morphogenesis. J Mammary Gland Biol Neoplasia. 5(1):7–17PubMedGoogle Scholar
  149. 149.
    Labrie F (2006) Dehydroepiandrosterone, androgens and the mammary gland. Gynecol Endocrinol. 22(3):118–30PubMedGoogle Scholar
  150. 150.
    Wilson CL et al (2006) Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue. Endocr Relat Cancer. 13(2):617–28PubMedGoogle Scholar
  151. 151.
    Woodward TL, Xie JW, Haslam SZ (1998) The role of mammary stroma in modulating the proliferative response to ovarian hormones in the normal mammary gland. J Mammary Gland Biol Neoplasia. 3(2):117–31PubMedGoogle Scholar
  152. 152.
    Lamarca HL, Rosen JM (2007) Estrogen regulation of mammary gland development and breast cancer: amphiregulin takes center stage. Breast Cancer Res. 9(4):304PubMedGoogle Scholar
  153. 153.
    Zhang HZ et al (2002) Estrogen mediates mammary epithelial cell proliferation in serum-free culture indirectly via mammary stroma-derived hepatocyte growth factor. Endocrinology. 143(9):3427–34PubMedGoogle Scholar
  154. 154.
    Soriano JV et al (1998) Roles of hepatocyte growth factor/scatter factor and transforming growth factor-beta1 in mammary glan ductal morphogenesis. J Mammary Gland Biol Neoplasia. 3(2):133–50PubMedGoogle Scholar
  155. 155.
    Pollard JW (2001) Tumour-stromal interactions. Transforming growth factor-beta isoforms and hepatocyte growth factor/scatter factor in mammary gland ductal morphogenesis. Breast Cancer Res. 3(4):230–7PubMedGoogle Scholar
  156. 156.
    Kamalati T et al (1999) HGF/SF in mammary epithelial growth and morphogenesis: in vitro and in vivo models. J Mammary Gland Biol Neoplasia. 4(1):69–77PubMedGoogle Scholar
  157. 157.
    Britten CD (2004) Targeting ErbB receptor signaling: a pan-ErbB approach to cancer. Mol Cancer Ther. 3(10):1335–42PubMedGoogle Scholar
  158. 158.
    Wiesen JF et al (1999) Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development. 126(2):335–44PubMedGoogle Scholar
  159. 159.
    Osin PP et al (1998) Breast development gives insights into breast disease. Histopathology. 33(3):275–83PubMedGoogle Scholar
  160. 160.
    Normanno N, Ciardiello F (1997) EGF-related peptides in the pathophysiology of the mammary gland. J Mammary Gland Biol Neoplasia. 2(2):143–51PubMedGoogle Scholar
  161. 161.
    Ruan W, Kleinberg DL (1999) Insulin-like growth factor 1 is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology. 140(11):5075–81PubMedGoogle Scholar
  162. 162.
    Wood TL, Yee D (2000) Introduction: IGFs and IGFBPs in the normal mammary gland and in breast cancer. J Mammary Gland Biol Neoplasia. 5(1):1–5PubMedGoogle Scholar
  163. 163.
    Ahmad T et al (2004) The mitogenic action of insulin-like growth factor I in normal human mammary epithelial cells requires the epidermal growth factor receptor tyrosine kinase. J Biol Chem. 279(3):1713–9PubMedGoogle Scholar
  164. 164.
    Wang W et al (2008) Glucocorticoid induced expression of connective tissue growth factor contributes to lactogenic differentiation of mouse mammary epithelial cells. J Cell Physiol. 214(1):38–46PubMedGoogle Scholar
  165. 165.
    Jiang WG et al (2004) Differential expression of the CCN family members Cyr61. CTGF and Nov in human breast cancer. Endocr Relat Cancer. 11(4):781–91PubMedGoogle Scholar
  166. 166.
    Anbazhagan R, Gusterson BA (1994) Prenatal factors may influence predisposition to breast cancer. Eur J Cancer. 30A(1):1–3PubMedGoogle Scholar
  167. 167.
    Hilakivi-Clarke L, de Assis S (2006) Fetal origins of breast cancer. Trends Endocrinol Metab. 17(9):340–8PubMedGoogle Scholar
  168. 168.
    Trichopoulos D, Lagiou P, Adami HO (2005) Towards an integrated model for breast cancer etiology: the crucial role of the number of mammary tissue-specific stem cells. Breast Cancer Res. 7(1):13–7PubMedGoogle Scholar
  169. 169.
    Hens JR, Wysolmerski JJ (2005) Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res. 7(5):220–4PubMedGoogle Scholar
  170. 170.
    Jolicoeur F (2005) Intrauterine breast development and the mammary myoepithelial lineage. J Mammary Gland Biol Neoplasia. 10(3):199–210PubMedGoogle Scholar
  171. 171.
    Arey L (1974) Developmental anatomy: a textbook and laboratory manual of embryology. Revised 7th ed. WB Saunders, PhiladelphiaGoogle Scholar
  172. 172.
    Russo J, Russo IH (1999) Mammary gland development In: Knobil E, Neill JD, (eds) Encyclopedia of reproduction San Diego: Academic Press.Google Scholar
  173. 173.
    Sadler TW (2003) Langman’s medical embryolgy., 9th edn. Lippincott Williams and Wilkins, BaltimoreGoogle Scholar
  174. 174.
    Robinson GW, Karpf AB, Kratochwil K (1999) Regulation of mammary gland development by tissue interaction. J Mammary Gland Biol Neoplasia. 4(1):9–19.PubMedGoogle Scholar
  175. 175.
    Anbazhagan R et al (1998) The development of epithelial phenotypes in the human fetal and infant breast. J Pathol. 184(2):197–206PubMedGoogle Scholar
  176. 176.
    Hovey RC, Trott JF, Vonderhaar BK (2002) Establishing a framework for the functional mammary gland: from endocrinology to morphology. J Mammary Gland Biol Neoplasia. 7(1):17–38PubMedGoogle Scholar
  177. 177.
    Tobon H, Slazar H (1974) Ultrastructure of the human mammary gland. I. Development of the fetal gland throughout gestation. J Clin Endocrinol Metab. 39(3):443–56PubMedGoogle Scholar
  178. 178.
    Kratochwil K, Schwartz P (1976) Tissue interaction in androgen response of embryonic mammary rudiment of mouse: identification of target tissue for testosterone. Proc Natl Acad Sci USA. 73(11):4041–4PubMedGoogle Scholar
  179. 179.
    Turner CW (1930) The anatomy of the mammary gland in cattle. II. Fetal development. Missouri Agric Exp Sta Res Bull. 160:5–39Google Scholar
  180. 180.
    Bocchinfuso WP et al (2000) Induction of mammary gland development in estrogen receptor-alpha knockout mice. Endocrinology. 141(8):2982–94PubMedGoogle Scholar
  181. 181.
    Aubert MJ, Grumbach MM, Kaplan SL (1975) The ontogenesis of human fetal hormones. III. Prolactin. J Clin Invest. 56(1):155–64PubMedGoogle Scholar
  182. 182.
    Keeling JW et al (2000) Oestrogen receptor alpha in female fetal. infant, and child mammary tissue. J Pathol. 191(4):449–51PubMedGoogle Scholar
  183. 183.
    Naccarato AG et al (2000) Bio-morphological events in the development of the human female mammary gland from fetal age to puberty. Virchows Arch. 436(5):431–8PubMedGoogle Scholar
  184. 184.
    Nathan B, Anbazhagan R, Clarkson P, Bartkova J (1994) Expression of BCL-2 in thedeveloping human fetal and infant breast. Histopathology. 24:73–6PubMedGoogle Scholar
  185. 185.
    Magdinier F et al (1999) BRCA1 expression during prenatal development of the human mammary gland. Oncogene. 18(27):4039–43PubMedGoogle Scholar
  186. 186.
    Casey TM et al (2007) Mammary epithelial cells treated concurrently with TGF-alpha and TGF-beta exhibit enhanced proliferation and death. Exp Biol Med (Maywood). 232(8):1027–40Google Scholar
  187. 187.
    Stull MA et al (2004) Growth factor regulation of cell cycle progression in mammary epithelial cells. J Mammary Gland Biol Neoplasia. 9(1):15–26PubMedGoogle Scholar
  188. 188.
    Streuli CH et al (1993) Extracellular matrix regulates expression of the TGF-beta 1 gene. J Cell Biol. 120(1):253–60PubMedGoogle Scholar
  189. 189.
    Chammas R et al (1994) Laminin and tenascin assembly and expression regulate HC11 mouse mammary cell differentiation. J Cell Sci. 107(Pt 4):1031–40PubMedGoogle Scholar
  190. 190.
    Dunbar ME, Wysolmerski JJ. The role of parathyroid hormone-related protein (PTHrP) in mammary development, lactation, and breast cancer. 1996 [cited; Available from: http://mammary.nih.gov/reviews/development/Wyso1001/slides/introduction.htmlGoogle Scholar
  191. 191.
    McKiernan J, Coyne J, Cahalane S (1988) Histology of breast development in early life. Arch Dis Child. 63(2):136–9PubMedGoogle Scholar
  192. 192.
    McKiernan JF, Hull D (1981) Breast development in the newborn. Arch Dis Childhood. 56:525–9Google Scholar
  193. 193.
    Russo J, Russo IH (1994) Toward a physiological approach to breast cancer prevention. Cancer Epidemiol Biomark Prev. 3(4):353–64Google Scholar
  194. 194.
    Russo J, Russ IH (1987) Development of the human mammary gland. In: Neville MD, Daniel C (eds) The mammary gland: development, regulation and function. Plenum, New YorkGoogle Scholar
  195. 195.
    McKiernan JF, Hull D (1981) Prolactin, maternal oestrogens, and breast development in the newborn. Arch Dis Child. 56(10):770–4PubMedGoogle Scholar
  196. 196.
    Schmidt IM et al (2002) Gender difference in breast tissue size in infancy: correlation with serum estradiol. Pediatr Res. 52(5):682–6PubMedGoogle Scholar
  197. 197.
    Pierce DF Jr et al (1993) Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev. 7(12A):2308–17PubMedGoogle Scholar
  198. 198.
    Russo I, Medado J, Russo J (1989) Endocrine influences on the mammary gland. In: Jones T, Mohr U, Hunt E (eds) Integument and mammary glands. Springer, BerlinGoogle Scholar
  199. 199.
    Humphreys RC (1999) Programmed cell death in the terminal end bud. J Mammary Gland Biol Neoplasia. 4(2):213–20PubMedGoogle Scholar
  200. 200.
    Humphreys RC et al (1996) Apoptosis in the terminal end bud of the murine mammary gland: a mechanism of ductal morphogenesis. Development. 122(12):4013–22PubMedGoogle Scholar
  201. 201.
    Britt K, Ashworth A, Smalley M (2007) Pregnancy and the risk of breast cancer. Endocr Relat Cancer. 14(4):907–33PubMedGoogle Scholar
  202. 202.
    Williams JM, Daniel CW (1983) Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol. 97(2):274–90PubMedGoogle Scholar
  203. 203.
    Topper YJ, Freeman CS (1980) Multiple hormone interactions in the developmental biology of the mammary gland. Physiol Rev. 60(4):1049–106PubMedGoogle Scholar
  204. 204.
    Anderson E, Clarke RB, Howell A (1998) Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia. 3(1):23–35PubMedGoogle Scholar
  205. 205.
    Laurence DJ, Monaghan P, Gusterson BA (1991) The development of the normal human breast. Oxf Rev Reprod Biol. 13:149–74PubMedGoogle Scholar
  206. 206.
    Russo J et al (2001) Cancer risk related to mammary gland structure and development. Microsc Res Tech. 52(2):204–23PubMedGoogle Scholar
  207. 207.
    Feldman M et al (1993) Evidence that the growth hormone receptor mediates differentiation and development of the mammary gland. Endocrinology. 133(4):1602–8PubMedGoogle Scholar
  208. 208.
    Marshman E, Streuli CH (2002) Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function. Breast Cancer Res. 4(6):231–9PubMedGoogle Scholar
  209. 209.
    Howlin J, McBryan J, Martin F (2006) Pubertal mammary gland development: insights from mouse models. J Mammary Gland Biol Neoplasia. 11(3–4):283–97PubMedGoogle Scholar
  210. 210.
    Going JJ et al (1988) Proliferative and secretory activity in human breast during natural and artificial menstrual cycles. Am J Pathol. 130(1):193–204PubMedGoogle Scholar
  211. 211.
    Ramakrishnan R, Khan SA, Badve S (2002) Morphological changes in breast tissue with menstrual cycle. Mod Pathol. 15(12):1348–56PubMedGoogle Scholar
  212. 212.
    Navarrete MA et al (2005) Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle. Breast Cancer Res. 7(3):R306–13PubMedGoogle Scholar
  213. 213.
    Andres AC, Strange R (1999) Apoptosis in the estrous and menstrual cycles. J Mammary Gland Biol Neoplasia. 4(2):221–8PubMedGoogle Scholar
  214. 214.
    Fanager H, Ree HJ (1974) Cyclic changes of human mammary gland epithelium in relation to the menstrual cycle-an ultrastructural study. Cancer. 34:574–85Google Scholar
  215. 215.
    Ferguson JE et al (1992) Changes in the extracellular matrix of the normal human breast during the menstrual cycle. Cell Tissue Res. 268(1):167–77PubMedGoogle Scholar
  216. 216.
    McCarty KS Jr et al (1982) Immunoglobulin localization in the normal human mammary gland: variation with the menstrual cycle. Am J Pathol. 107(3):322–6PubMedGoogle Scholar
  217. 217.
    Kass R, Mancino AT, Rosenbloom AL, Klimberg VS, Bland KI (2004) Breast physiology: normal and abnormal development and function. In: Bland KI, Copeland EM III (eds) The breast: comprehensive management of benign and malignant disorders. Saunders, St. Louis, MissouriGoogle Scholar
  218. 218.
    Silva JS et al (1983) Menstrual cycle-dependent variations of breast cyst fluid proteins and sex steroid receptors in the normal human breast. Cancer. 51(7):1297–302PubMedGoogle Scholar
  219. 219.
    Fabris G et al (1987) Pathophysiology of estrogen receptors in mammary tissue by monoclonal antibodies. J Steroid Biochem. 27:171–6PubMedGoogle Scholar
  220. 220.
    Dabrosin C (2005) Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle. J Endocrinol. 187(1):103–8PubMedGoogle Scholar
  221. 221.
    Gompel A et al (1996) Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue during the menstrual cycle. Breast Cancer Res Treat. 38(2):227–35PubMedGoogle Scholar
  222. 222.
    Nevalainen MT et al (2002) Basal activation of transcription factor signal transducer and activator of transcription (Stat5) in nonpregnant mouse and human breast epithelium. Mol Endocrinol. 16(5):1108–24PubMedGoogle Scholar
  223. 223.
    Ham AW (1969) Histology. 6th edn. JB Lippincott, PhiladelphiaGoogle Scholar
  224. 224.
    Russell TD et al (2007) Cytoplasmic lipid droplet accumulation in developing mammary epithelial cells: roles of adipophilin and lipid metabolism. J Lipid Res. 48(7):1463–75PubMedGoogle Scholar
  225. 225.
    Morroni M et al (2004) Reversible transdifferentiation of secretory epithelial cells into adipocytes in the mammary gland. Proc Natl Acad Sci USA. 101(48):16801–6PubMedGoogle Scholar
  226. 226.
    Piliero SJ, Jacobs MS, Wischnitzer S (1965) Atlas of histology. JB Lippincott, PhiladelphiaGoogle Scholar
  227. 227.
    Medina D (2005) Mammary developmental fate and breast cancer risk. Endocr Relat Cancer. 12(3):483–95PubMedGoogle Scholar
  228. 228.
    Balogh GA et al (2006) Genomic signature induced by pregnancy in the human breast, Int J Oncol. 28(2):399–410PubMedGoogle Scholar
  229. 229.
    Popnikolov N et al (2001) Reconstituted normal human breast in nude mice: effect of host pregnancy environment and human chorionic gonadotropin on proliferation. J Endocrinol. 168(3):487–96PubMedGoogle Scholar
  230. 230.
    Numan M (1994) Maternal behavior. In: Knobil E, Neill JD (eds) The physiology of reproduction. Raven, New York, pp. 221–302Google Scholar
  231. 231.
    Eliassen AH, Tworoger SS, Hankinson SE (2007) Reproductive factors and family history of breast cancer in relation to plasma prolactin levels in premenopausal and postmenopausal women. Int J Cancer. 120(7):1536–41PubMedGoogle Scholar
  232. 232.
    Blakely CM et al (2006) Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by prennancy. Cancer Res. 66(12):6421–31PubMedGoogle Scholar
  233. 233.
    Russo J et al (2005) Breast differentiation and its implication in cancer prevention. Clin Cancer Res. 11(2 Pt 2): 931s–6sPubMedGoogle Scholar
  234. 234.
    Russo J et al (2005) The protective role of pregnancy in breast cancer. Breast Cancer Res. 7(3):131–42PubMedGoogle Scholar
  235. 235.
    Jackson D, Bresnick J, Dickson C (1997) A role for fibroblast growth factor signaling in the lobuloalveolar development of the mammary gland. J Mammary Gland Biol Neoplasia. 2(4):385–92PubMedGoogle Scholar
  236. 236.
    Laud K et al (2001) Expression of BRCA1 gene in ewe mammary epithelial cells during pregnancy: regulation by growth hormone and steroid normones. Eur J Endocrinol. 145(6):763–70PubMedGoogle Scholar
  237. 237.
    Furuta S et al (2005) Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells. Proc Natl Acad Sci USA. 102(26):9176–81PubMedGoogle Scholar
  238. 238.
    Burkitt HG, Young B, Heathe JW (1993) Wheater’s functional histology, a text and colour atlas. 3rd edn. Churchill Livingstone, EdinburghGoogle Scholar
  239. 239.
    Espinosa LA et al (2005) The lactating breast: contrastenhanced MR imaging of normal tissue and cancer. Radiology. 237(2):429–36PubMedGoogle Scholar
  240. 240.
    Forsyth I. Mammary gland, overview. In: Knobil E, Neill JD, editors. Encyclopedia of reproduction. Academic; 1999 p. 81–88Google Scholar
  241. 241.
    Neville MC. Milk secretion: an overview. 1998 [cited 07/31/2007]; Available from: http://mammary.nih.gov/ Reviews/lactation/neville001/index.htmlGoogle Scholar
  242. 242.
    Itoh M, Bissell MJ (2003) The organization of tight junctions in epithelia: implications for mammary gland biology and breast tumorigenesis. J Mammary Gland Biol Neoplasia. 8(4):449–62PubMedGoogle Scholar
  243. 243.
    Young B, Wheater PR (2006) Wheater’s functional histology: a text and colour atlas., 5th edn. Churchill Livingstone Elsevier, Oxford, p. 437Google Scholar
  244. 244.
    Kolb AF (2002) Engineering immunity in the mammary gland. J Mammary Gland Biol Neoplasia. 7(2):123–34PubMedGoogle Scholar
  245. 245.
    Uauy R, De Andraca I (1995) Human milk and breast feeding for optimal mental development. J Nutr. 125(8 Suppl):2278S–80SPubMedGoogle Scholar
  246. 246.
    Lawson M (2007) Contemporary aspects of infant feeding. Paediatr Nurs. 19(2):39–46PubMedGoogle Scholar
  247. 247.
    Owen CG et al (2003) Effect of breast feeding in infancy on blood pressure in later life: systematic review and meta-analysis. BMJ. 327(7425):1189–95PubMedGoogle Scholar
  248. 248.
    Martin RM et al (2005) Breast-feeding and cancer: the Boyd Orr cohort and a systematic review with meta-analysis. J Natl Cancer Inst. 97(19):1446–57PubMedGoogle Scholar
  249. 249.
    Frank JW, Newman J (1993) Breast-feeding in a polluted world: uncertain risks, clear benefits. CMAJ. 149(1):33–7PubMedGoogle Scholar
  250. 250.
    Rudolph MC et al (2007) Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine. Physiol Genomics. 28(3):323–36PubMedGoogle Scholar
  251. 251.
    Villalpando S, del Prado M (1999) Interrelation among dietary energy and fat intakes, maternal body fatness, and milk total lipid in humans. J Mammary Gland Biol Neoplasia. 4(3):285–95PubMedGoogle Scholar
  252. 252.
    Neville MC (2005) Calcium secretion into milk. J Mammary Gland Biol Neoplasia. 10(2):119–28PubMedGoogle Scholar
  253. 253.
    Keenan TS, Franke WW, Mather IH, Morre DJ (1978) Endomembrane composition and function in milk formation. In: Larson BL (ed) Lactation. Academic, New York, p 105Google Scholar
  254. 254.
    Linzell JL, Peaker M (1971) Mechanism of milk secretion. Physiol Rev. 51(3):564–97PubMedGoogle Scholar
  255. 255.
    Neville MC (1990) The physiological basis of milk secretion. Ann N Y Acad Sci. 586:1–11PubMedGoogle Scholar
  256. 256.
    Fleishaker JC, McNamara PJ (1988) In vivo evaluation in the lactating rabbit of a model for xenobiotic distribution into breast milk. J Pharmacol Exp Ther. 244(3):919–24PubMedGoogle Scholar
  257. 257.
    Hunziker W, Kraehenbuhl JP (1998) Epithelial transcytosis of immunoglobulins. J Mammary Gland Biol Neoplasia. 3(3):287–302PubMedGoogle Scholar
  258. 258.
    Csontos K et al (1979) Elevated plasma beta-endorphin levels in pregnant women and their neonates. Life Sci. 25(10):835–44PubMedGoogle Scholar
  259. 259.
    Clevenger CV, Plank TL (1997) Prolactin as an autocrine/paracrine factor in breast tissue. J Mammary Gland Biol Neoplasia. 2(1):59–68PubMedGoogle Scholar
  260. 260.
    Mol JA et al (2000) Progestin-induced mammary growth hormone (GH) production. Adv Exp Med Biol. 480:71–6PubMedGoogle Scholar
  261. 261.
    McNeilly AS et al (1983) Release of oxytocin and prolactin in response to suckling. Br Med J (Clin Res Ed). 286(6361):257–9Google Scholar
  262. 262.
    Martin RH, Oakey RE (1982) The role of antenatal oestrogen in postpartum human lactogenesis: evidence from oestrogen-deficient pregnancies. Clin Endocrinol (Oxford England). 17(4):403–8Google Scholar
  263. 263.
    Daly SE et al (1996) Frequency and degree of milk removal and the short-term control of human milk synthesis. Exp Physiol. 81(5):861–75PubMedGoogle Scholar
  264. 264.
    Hadsell D, George J, Torres D (2007) The declining phase of lactation: peripheral or central, programmed or pathological? J Mammary Gland Biol Neoplasia. 12(1):59–70PubMedGoogle Scholar
  265. 265.
    Itahana Y et al (2007) Regulation of clusterin expression in mammary epithelial cells. Exp Cell Res. 313(5):943–51PubMedGoogle Scholar
  266. 266.
    Mennella JA, Pepino MY, Teff KL (2005) Acute alcohol consumption disrupts the hormonal milieu of lactating women. J Clin Endocrinol Metab. 90(4):1979–85PubMedGoogle Scholar
  267. 267.
    Butte NF, Hopkinson JM (1998) Body composition changes during lactation are highly variable among women. J Nutr. 128(2) Suppl:381S–5SPubMedGoogle Scholar
  268. 268.
    Ganong’s Review of Medical Physiology. 23rd ed. Lange. 2009. p. 452Google Scholar
  269. 269.
    Dewey KG (1998) Effects of maternal caloric restriction and exercise during lactation. J Nutr. 128(2 Suppl):386S–9SPubMedGoogle Scholar
  270. 270.
    Wysolmerski J (2005) Calcium handling by the lactating breast and its relationship to calcium-related complications of breast cancer. J Mammary Gland Biol Neoplasia. 10(2):101–3PubMedGoogle Scholar
  271. 271.
    Kovacs CS (2005) Calcium and bone metabolism during pregnancy and lactation. J Mammary Gland Biol Neoplasia. 10(2):105–18PubMedGoogle Scholar
  272. 272.
    Wilde CJ, Knight CH, Flint DJ (1999) Control of milk secretion and apoptosis during mammary involution. J Mammary Gland Biol Neoplasia. 4(2):129–36PubMedGoogle Scholar
  273. 273.
    Talhouk RS, Bissell MJ, Werb Z (1992) Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 118(5):1271–82PubMedGoogle Scholar
  274. 274.
    Marti A et al (1999) Transcription factor activities and gene expression during mouse mammary gland involution. J Mammary Gland Biol Neoplasia. 4(2):145–52PubMedGoogle Scholar
  275. 275.
    Stein T, Salomonis N, Gusterson BA (2007) Mammary gland involution as a multi-step process. J Mammary Gland Biol Neoplasia. 12(1):25–35PubMedGoogle Scholar
  276. 276.
    Jaggi R. Morphological changes during programmed cell death (PCD) in the involuting mouse mammary gland. 1996 [cited; Available from: http://mammary.nih.gov/reviews/development/Jaggi001/index.htmlGoogle Scholar
  277. 277.
    Baxter FO, Neoh K, Tevendale MC (2007) The beginning of the end: death signaling in early involution. J Mammary Gland Biol Neoplasia. 12(1):3–13PubMedGoogle Scholar
  278. 278.
    Thorburn A (2007) Apoptosis and autophagy: regulatory connections between two supposedly different processes. Apoptosis. 13(1):1–9Google Scholar
  279. 279.
    Atabai K, Sheppard D, Werb Z (2007) Roles of the innate immune system in mammary gland remodeling during involution. J Mammary Gland Biol Neoplasia. 12(1):37–45PubMedGoogle Scholar
  280. 280.
    Fadok VA (1999) Clearance: the last and often forgotten stage of apoptosis. J Mammary Gland Biol Neoplasia. 4(2):203–11PubMedGoogle Scholar
  281. 281.
    Watson CJ (2006) Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ. Breast Cancer Res. 8(2):203PubMedGoogle Scholar
  282. 282.
    Streuli CH, Gilmore AP (1999) Adhesion-mediated signaling in the regulation of mammary epithelial cell survival. J Mammary Gland Biol Neoplasia. 4(2):183–91PubMedGoogle Scholar
  283. 283.
    Martinez-Hernandez A, Fink LM, Pierce GB (1976) Removal of basement membrane in the involuting breast. Lab Invest, 34(5):455–62PubMedGoogle Scholar
  284. 284.
    Simpson HW et al (2002) Pregnancy postponement and childlessness leads to chronic hypervascularity of the breasts and cancer risk. Br J Cancer. 87(11):1246–52PubMedGoogle Scholar
  285. 285.
    Flint DJ, Tonner E, Allan GJ (2000) Insulin-like growth factor binding proteins: IGF-dependent and-independent effects in the mammary gland. J Mammary Gland Biol Neoplasia. 5(1):65–73PubMedGoogle Scholar
  286. 286.
    Lochrie JD et al (2006) Insulin-like growth factor binding protein (IGFBP)-5 is up-regulated during both differentiation and apoptosis in primary cultures of mouse mammary epithelial cells. J Cell Physiol. 207(2):471–9PubMedGoogle Scholar
  287. 287.
    Watson CJ, Burdon TG (1996) Prolactin signal transduction mechanisms in the mammary gland: the role of the Jak/Stat pathway. Rev Reprod. 1(1):1–5PubMedGoogle Scholar
  288. 288.
    Hu X et al (2002) Leptin-a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst. 94(22):1704–11PubMedGoogle Scholar
  289. 289.
    Dontu G et al (2004) Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells. Breast Cancer Res. 6(6):R605–15PubMedGoogle Scholar
  290. 290.
    Dontu G, Wicha MS (2005) Survival of mammary stem cells in suspension culture: implications for stem cell biology and neoplasia. J Mammary Gland Biol Neoplasia. 10(1):75–86PubMedGoogle Scholar
  291. 291.
    Rowley M, Grothey E, Couch FJ (2004) The role of Tbx2 and Tbx3 in mammary development and tumorigenesis. J Mammary Gland Biol Neoplasia. 9(2):109–18PubMedGoogle Scholar
  292. 292.
    Kouros-Mehr H et al (2006) GATA-3 maintains the differentiation of the luminal cell fate in the mammary gland. Cell. 127(5):1041–55PubMedGoogle Scholar
  293. 293.
    Lewis MT, Veltmaat JM (2004) Next stop, the twilight zone: hedgehog network regulation of mammary gland development. J Mammary Gland Biol Neoplasia. 9(2):165–81PubMedGoogle Scholar
  294. 294.
    Hatsell S, Frost AR (2007) Hedgehog signaling in mammary gland development and breast cancer. J Mammary Gland Biol Neoplasia. 12(2–3):163–73PubMedGoogle Scholar
  295. 295.
    Groner B (2002) Transcription factor regulation in mammary epithelial cells. Domest Anim Endocrinol. 23(1–2):25–32PubMedGoogle Scholar
  296. 296.
    Zhou J et al (2005) Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation. Embo J. 24(3):635–44PubMedGoogle Scholar
  297. 297.
    Puppin C et al (2006) HEX expression and localization in normal mammary gland and breast carcinoma. BMC Cancer. 6:192PubMedGoogle Scholar
  298. 298.
    van Genderen C et al (1994) Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 8(22): 2691–703PubMedGoogle Scholar
  299. 299.
    Davenport TG, Jerome-Majewska LA, Papaioannou VE (2003) Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development, 130(10):2263–73PubMedGoogle Scholar
  300. 300.
    Satokata I et al (2000) Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet. 24(4):391–5PubMedGoogle Scholar
  301. 301.
    Dunbar ME et al (1999) Parathyroid hormone-related protein signaling is necessary for sexual dimorphism during embryonic mammary development. Development. 126(16):3485–93PubMedGoogle Scholar
  302. 302.
    Kim H, Laing M, Muller W (2005) c-Src-null mice exhibit defects in normal mammary gland development and ERalpha signaling. Oncogene. 24(36):5629–36PubMedGoogle Scholar
  303. 303.
    Lydon JP et al (1995) Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Genes Dev. 9((18):2266–78Google Scholar
  304. 304.
    Horseman ND et al (1997) Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. Embo J. 16(23):6926–35PubMedGoogle Scholar
  305. 305.
    Pollard JW, Hennighausen L (1994) Colony stimulating factor 1 is required for mammary gland development during pregnancy. Proc Natl Acad Sci USA. 91(20):9312–6PubMedGoogle Scholar
  306. 306.
    Fantl V et al (1995) Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 9(19):2364–72PubMedGoogle Scholar
  307. 307.
    Stinnakre MG et al (1994) Creation and phenotypic analysis of alpha-lactalbumin-deficient mice. Proc Natl Acad Sci USA. 91(14):6544–8PubMedGoogle Scholar
  308. 308.
    Triplett AA et al (2005) Expression of the whey acidic protein (Wap) is necessary for adequate nourishment of the offspring but not functional differentiation of mammary epithelial cells. Genesis. 43(1):1–11PubMedGoogle Scholar
  309. 309.
    Wagner KU et al (1997) Oxytocin and milk removal are required for postpartum mammary gland development. Genes Funct. 1(4):233–44PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Martha C. Johnson
    • 1
  1. 1.Uniformed Services University of the Health SciencesBethesdaUSA

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