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Epithelial Progenitors in the Normal Human Mammary Gland

Journal of Mammary Gland Biology and Neoplasia volume 10, pages 49–59 (2005)Cite this article

Abstract

The human mammary gland is organized developmentally as a hierarchy of progenitor cells that become progressively restricted in their proliferative abilities and lineage options. Three types of human mammary epithelial cell progenitors are now identified. The first is thought to be a luminal-restricted progenitor; in vitro under conditions that support both luminal and myoepithelial cell differentiation, this cell produces clones of differentiating daughter cells that are exclusively positive for markers characteristic of luminal cells produced in vivo (i.e., keratins 8/18 and 19, epithelial cell adhesion molecule [EpCAM] and MUC1). The second type is a bipotent progenitor. It is identified by its ability to produce “mixed” colonies in single cell assays. These colonies contain a central core of cells expressing luminal markers surrounded by cells with a morphology and markers (e.g., keratin 14+) characteristic of myoepithelial cells. Serial passage in vitro of an enriched population of bipotent progenitors promotes the expansion of a third type of progenitor that is thought to be myoepithelial-restricted because it only produces cells with myoepithelial features. Luminal-restricted and bipotent progenitors can prospectively be isolated as distinct subpopulations from freshly dissociated suspensions of normal human mammary cells. Both are distinguished from many other cell types in mammary tissue by their expression of EpCAM and CD49f (α6 integrin). They are distinguished from each other by their differential expression of MUC1, which is expressed at much higher levels on the luminal progenitors. To relate the role of these progenitors to the generation of the three-dimensional tubuloalveolar structure of the mammary tree produced in vivo, we propose a model in which the commitment to the luminal versus the myoepithelial lineage may play a determining role in the generation of alveoli and ducts.

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Abbreviations

EpCAM:

epithelial cell adhesion molecule

TDLU:

terminal ductal lobular unit

TEB:

terminal end bud

SMA:

smooth muscle actin

SLC:

small light cell

K:

keratin

MaSC:

mammary stem cell

HMEC:

human mammary epithelial cell

Ma-CFC:

mammary colony-forming cell

Ma-CFCLu:

luminal-restricted progenitor

Ma-CFC-Me:

myoepithelialrestricted progenitor

Ma-CFC-LuMe:

bipotent progenitor

CALLA:

common acute lymphoblastic leukemia antigen

ESA:

epithelial specific antigen

BGA2:

histo-blood group antigen H type 2

EGF:

epidermal growth factor

FACS:

fluorescenceactivated cell sorting

References

  1. Russo J, Russo IH. Development of the human mammary gland. In: Neville MC and Daniel CW, editors. The mammary gland: Development, regulation and function. New York (NY): Plenum; 1987. p. 67–93.

    Google Scholar 

  2. Emerman JT, Vogl AW. Cell size and shape changes in the myoepithelium of the mammary gland during differentiation. Anat Rec 1986;216:405–15.

    Article  CAS  PubMed  Google Scholar 

  3. Anderson TJ, Ferguson DJP, Raab GM. Cell turnover in the “resting” human breast: Influence of parity, contraceptive pill, age and laterality. Br J Cancer 1982;46:376–82.

    CAS  Google Scholar 

  4. Joshi K, Smith JA, Perusinghe N, Monoghan P. Cell proliferation in human mammary epithelium. Differential contribution by epithelial and myoepithelial cells. Am J Pathol 1986;124:199–206.

    CAS  Google Scholar 

  5. Smith GH, Medina D. A morphologically distinct candidate for an epithelial stem cell in the mouse mammary gland. J Cell Sci 1988;89:173–83.

    Google Scholar 

  6. Ferguson DJP. An ultrastructural study of mitosis and cytokinesis in normal “resting” human breast. Cell Tissue Res 1988;252: 581–87.

    Article  CAS  PubMed  Google Scholar 

  7. Sapino A, Macri L, Gugliotta P, Bussolati G. Immunocytochemical identification of proliferating cell types in mouse mammary gland. J Histochem Cytochem 1990;38:1541–47.

    CAS  PubMed  Google Scholar 

  8. Perusinghe NP, Monaghan P, O’Hare MJ, Ashley S, Gusterson BA. Effects of growth factors on proliferation of basal and luminal cells in human breast epithelial explants in serum-free culture. In Vitro Cell Dev Biol 1992;28A:90–96.

    CAS  PubMed  Google Scholar 

  9. Chepko G, Smith GH. Three division-competent, structurally-distinct cell populations contribute to murine mammary epithelial renewal. Tissue Cell 1997;29:239–53.

    CAS  PubMed  Google Scholar 

  10. Zeps N, Bentel JM, Papadimitriou JM, D’Antuono MF, Dawkins HJ. Estrogen receptor-negative epithelial cells in mouse mammary gland development and growth. Differentiation 1998;62:221–26.

    Article  CAS  PubMed  Google Scholar 

  11. Clarke RB, Howell A, Anderson E. Estrogen sensitivity of normal human breast tissue in vivo and implanted into athymic nude mice: Analysis of the relationship between estrogen-induced proliferation and progesterone receptor expression. Breast Cancer Res Treat 1997;45:121–33.

    Article  CAS  PubMed  Google Scholar 

  12. Williams JM, Daniel CW. Mammary ductal elongation: Differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol 1983; 97:274–90.

    Article  CAS  PubMed  Google Scholar 

  13. Rudland PS, Barraclough R, Fernig DG, Smith JA. Mammary stem cells in normal development and cancer. In: Potten C, editor. Stem cells. San Diego (CA): Academic Press; 1997. p. 147–232.

    Google Scholar 

  14. Sapino A, Macri L, Gugliotta P, Pacchioni D, Liu YJ, Medina D and Bussolati G. Immunophenotypic properties and estrogen dependency of budding structures in the developing mouse mammary gland. Differentiation 1993;55:13–18.

    Article  CAS  PubMed  Google Scholar 

  15. Smith GH, Strickland P, Daniel CW. Putative epithelial stem cell loss corresponds with mammary growth senescence. Cell Tissue Res 2002;310:313–20.

    Article  PubMed  Google Scholar 

  16. Bartek J, Bartkova J, Taylor-Papadimitriou J. Keratin 19 expression in the adult and developing human mammary gland. Histochem J 1990;22:537–44.

    Article  CAS  PubMed  Google Scholar 

  17. Daniel CW, DeOme KB, Young JT, Blair PB, Faulkin LJ. The in vivo life span of normal and preneoplastic mouse mammary glands: A serial transplantation study. Proc Natl Acad Sci USA 1968;61:52–60.

    Google Scholar 

  18. Smith GH. Experimental mammary epithelial morphogenesis in an in vivo model: Evidence for distinct cellular progenitors of the ductal and lobular phenotype. Breast Cancer Res Treat 1996;39:21–31.

    CAS  PubMed  Google Scholar 

  19. Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development 1998;125:1921–30.

    CAS  PubMed  Google Scholar 

  20. Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA. Sca-1 (pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol 2002;245:42–56.

    Article  CAS  PubMed  Google Scholar 

  21. Stingl J, Ricketson I, Choi D, Eaves CJ. Phenotypic characterization of mouse mammary stem and progenitor cells. Proc Am Assoc Cancer Res 2004;45:641–2.

    Google Scholar 

  22. O’Hare MJ, Ormerod MG, Monaghan P, Lane EB, Gusterson BA. Characterization in vitro of luminal and myoepithelial cells isolated from the human mammary gland by cell sorting. Differentiation 1991;46:209–21.

    CAS  PubMed  Google Scholar 

  23. Kao CY, Nomata K, Oakley CS, Welsch CW, Chang CC. Two types of normal human breast epithelial cells derived from reduction mammoplasty: Phenotypic characterization and response to SV40 transfection. Carcinogenesis 1995;16:531–38.

    CAS  PubMed  Google Scholar 

  24. Kao CY, Oakley CS, Welsch CW, Chang CC. Growth requirements and neoplastic transformation of two types of normal human breast epithelial cells derived from reduction mammoplasty. In Vitro Cell Dev Biol Anim 1997;33:282–88.

    CAS  PubMed  Google Scholar 

  25. Stingl J, Eaves CJ, Kuusk U, Emerman JT. Phenotypic and functional characterization in vitro of a multipotent epithelial cell present in the normal adult human breast. Differentiation 1998;63:201–13.

    Article  CAS  PubMed  Google Scholar 

  26. Stingl J, Eaves CJ, Emerman JT. Characterization of normal human breast epithelial cell subpopulations isolated by fluorescence-activated cell sorting and their clonogenic growth in vitro. In: Ip M and Asch BB, editors. Methods in mammary gland biology and breast cancer research. New York (NY): Kluwer Academic; 2000. p. 177–93.

    Google Scholar 

  27. Matouskova E, Dudorkinova D, Krasna L, Vesely P. Temporal in vitro expansion of the luminal lineage of human mammary epithelial cells achieved with the 3T3 feeder layer technique. Breast Cancer Res Treat 2000;60:241–49.

    Article  CAS  PubMed  Google Scholar 

  28. Stingl J, Zandieh I, Eaves CJ, Emerman JT. Characterization of bipotent mammary epithelial progenitor cells in normal adult human tissue. Breast Cancer Res Treat 2001:67:93–109.

    Article  CAS  PubMed  Google Scholar 

  29. Gudjonsson T, Villadsen R, Nielsen HL, Ronnov-Jessen L, Bissell MJ, Petersen OW. Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties. Gene Dev 2002;16:693–706.

    Article  CAS  PubMed  Google Scholar 

  30. Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS. in vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Gene Dev 2003;17:1253–70.

    Google Scholar 

  31. Clayton H, Titley I, Vivanco MM. Growth and differentiation of progenitor/stem cells derived from the human mammary gland. Exp Cell Res 2004;297:444–60.

    Article  CAS  PubMed  Google Scholar 

  32. Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G. A monoclonal antibody against α-smooth muscle actin: A new probe for smooth muscle differentiation. J Cell Biol 1986;103:2787–96.

    Article  CAS  PubMed  Google Scholar 

  33. Gusterson BA, Monaghan P, Mahendran R, Ellis J, O’Hare MJ. Identification of myoepithelial cells in human and rat breasts by anti-common acute lymphoblstic leukemia antigen antibody A12. J Natl Cancer Inst 1986;77:343–49.

    CAS  PubMed  Google Scholar 

  34. Koukoulis GK, Virtanen I, Horhonen M, Laitinen L, Quaranta V, Gould VE. Immunohistochemical localization of integrins in the normal, hyperplastic, and neoplastic breast. Am J Pathol 1991;139:787–99.

    CAS  Google Scholar 

  35. Batistatou A, Stefanou D, Arkoumani E, Agnantis NJ. The usefulness of p63 as a marker of breast myoepithelial cells. In Vivo 2003;17:573–76.

    PubMed  Google Scholar 

  36. Guelstein VI, Tchypyscheva TA, Ermilova VD, Litvinova LV, Troyanovsky SM, Bannikov GA. Monoclonal antibody mapping of keratins 8 and 17 and of vimentin in normal human mammary gland, benign tumors, dysplasias and breast cancer. Int J Cancer 1988;42:147–53.

    CAS  PubMed  Google Scholar 

  37. Fox SB, Fawcett J, Jackson DG, Collins I, Gatter KC, Harris AL, Gearing A, Simmons DL. Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms. Cancer Res 1994;54:4539–46.

    CAS  PubMed  Google Scholar 

  38. Taylor-Papadimitriou J, Stampfer M, Bartek J, Lewis A, Boshell M, Lane EB, Leigh IM. Keratin expression in human mammary epithelial cells cultured from normal and malignant tissue: Relation to in vivo phenotypes and influence of medium. J Cell Sci 1989;94:403–13.

    PubMed  Google Scholar 

  39. Jones C, Mackay A, Grigoriadis A, Cossu A, Reis-Filho JS, Fulford L, Dexter T, Davies S, Bulmer K, Ford E, Parry S, Budroni M, Palmieri G, Neville AM, O’Hare MJ, Lakhani SR. Expression profiling of purified normal human luminal and myoepithelial breast cells: Identification of novel prognostic markers for breast cancer. Cancer Res 2004;64:3037–45.

    CAS  PubMed  Google Scholar 

  40. Corbeil D, Roper K, Hellwig A, Tavian M, Miraglia S, Watt SM, Simmons PJ, Peault B, Buck DW, Huttner WB. The human AC133 hematopoietic stem cell antigen is also expressed in epithelial cells and targeted to plasma membrane protrusions. J Biol Chem 2000;275:5512–20.

    CAS  PubMed  Google Scholar 

  41. Taylor-Papadimitriou J, Burchell JM, Punkett T, Graham R, Correa I, Miles D, Smith M. MUC1 and the immunobiology of cancer. J Mammary Gland Biol Neoplasia 2002;7:209–21.

    PubMed  Google Scholar 

  42. Latza U, Niedobitek G, Schwarting R, Nekarda H, Stein H. Ber-EP4: New monoclonal antibody which distinguishes epithelia from mesothelia. J Clin Pathol 1990;43:213–19.

    CAS  PubMed  Google Scholar 

  43. Gompel A, Martin A, Simon P, Schoevaert D, Plu-Bureau G, Hugol D, Audouin J, Leygue E, Truc JB, Poitout P. Epidermal growth factor receptor and c-erbB-2 expression in normal breast tissue during the menstrual cycle. Breast Cancer Res Treat 1996;38:227–35.

    CAS  PubMed  Google Scholar 

  44. Purkis PE, Steel JB, Mackenzie IC, Nathrath WBJ, Leigh IM, Lane EB. Antibody markers of basal cells in complex epithelia. J Cell Sci 1990;97:39–50.

    PubMed  Google Scholar 

  45. Rudland PS, Hughes CM. Immunocytochemical identification of cell types in human mammary gland: Variation in cellular markers are dependent on glandular topography and differentiation. J Histochem Cytochem 1989;37:1087–100.

    CAS  PubMed  Google Scholar 

  46. Moll R, Franke WW, Schiller DL. The catalogue of human cytokeratins: Patterns of expression in normal epithelial, tumors and cultured cells. Cell 1982;31:11–24.

    CAS  PubMed  Google Scholar 

  47. Edwards PAW, Brooks IM. Antigenic subsets of human breast epithelial cells distinguished by monoclonal antibodies. J Histochem Cytochem 1984;32:531–37.

    CAS  PubMed  Google Scholar 

  48. Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res 1987;47:2883–91.

    CAS  PubMed  Google Scholar 

  49. Pechoux C, Gudjonsson T, Ronnov-Jessen L, Bissell MJ, Petersen OW. Human mammary luminal cells contain progenitors to myoepithelial cells. Dev Biol 1999;206:88–99.

    Article  CAS  PubMed  Google Scholar 

  50. Idris N, Carothers Carraway CA, Carraway KL. Differential localization of erbB2 in different tissues of the rat female reproductive tract: Implications for the use of specific antibodies for erbB2 analysis. J Cell Physiol 2001;189:162–70.

    CAS  PubMed  Google Scholar 

  51. Stingl J, Emerman JT, Eaves CJ. Enzymatic dissociation and culture of normal human mammary tissue to detect progenitor activity. In: Helgason CD and Miller CL, editors. Methods in molecular biology: Basic cell culture protocols, Vol 290, 3rd ed. Totowa (NJ): Humana Press; 2004. p. 249–64.

    Google Scholar 

  52. Russo J, Mills MJ, Moussalli MJ, Russo IH. Influence of human breast development on the growth properties of primary cultures. In Vitro Cell Dev Biol 1989;25:643–49.

    CAS  PubMed  Google Scholar 

  53. Romanov SR, Kozakiewicz, BK, Holst CR, Stampfer MR, Haupt LM and Tlsty TD. Normal human mammary epithelial cells spontaneously escape senescence and acquire genomic changes. Nature 2001;409:633–37.

    CAS  PubMed  Google Scholar 

  54. Karsten U, Papsdorf F, Pauly A, Vojtesek B, Moll R, Lane EB, Clausen H, Stosiek P, Kasper M. Subtypes of non-transformed human mammary epithelial cells cultured in vitro: Histo-blood group antigen H type 2 defines basal cell-derived cells. Differentiation 1993;54:55–66.

    CAS  PubMed  Google Scholar 

  55. Stingl J. in vitro phenotypic and functional characterization of breast epithelial progenitors present in the normal adult human breast. PhD Thesis, Department of Anatomy, University of British Columbia, 2000.

  56. Petersen OW, van Deurs B. Growth factor control of myoepithelial-cell differentiation in cultures of human mammary gland. Differentiation 1998;39:197–215.

    Google Scholar 

  57. Schaefer FV, Custer RP, Sorof S. Squamous metaplasia in human breast culture: Induction by cyclic adenine nucleotide and prostaglandins, and influence of menstrual cycle. Cancer Res 1983;43:279–86.

    CAS  PubMed  Google Scholar 

  58. Tlsty TD, Romanov SR, Kozakiewicz BK, Holst CR, Haupt LM, Crawford YG. Loss of chromosomal integrity in human mammary epithelial cells subsequent to escape from senescence. J Mammary Gland Biol Neoplasia 2001;6:235–43.

    CAS  PubMed  Google Scholar 

  59. Dundas SR, Ormerod MG, Gusterson BA, O’Hare MJ. Characterization of luminal and basal cells flow-sorted from the adult rat mammary parenchyma. J Cell Sci 1991;100:459–71.

    PubMed  Google Scholar 

  60. Smalley MJ, Titley J, O’Hare MH. Clonal characterization of mouse mammary luminal epithelial and myoepithelial cells separated by fluorescence-activated cell sorting. In Vitro Cell Dev Biol Anim 1998;34:711–21.

    CAS  PubMed  Google Scholar 

  61. Smalley MJ, Titley J, Paterson H, Perusinghe N, Clarke C, O’Hare MJ. Differentiation of separated mouse mammary luminal epithelial and myoepithelial cells cultured on EHS matrix analyzed by indirect immunoflourescence of cytoskeletal antigens. J Histochem Cytochem 1999;47:1513–24.

    CAS  PubMed  Google Scholar 

  62. Ethier SP, Mahacek ML, Gullick WJ, Frank TJ, Weber BL. Differential isolation of normal luminal mammary epithelial cells and breast cancer cells from primary and metastatic sites using selective media. Cancer Res 1993;53:627–35.

    CAS  PubMed  Google Scholar 

  63. Ethier SP. Human breast cancer cell lines as models of growth regulation and disease progression. J Mammary Gland Biol Neoplasia 1996;1:111–21.

    CAS  PubMed  Google Scholar 

  64. Gomm JJ, Coope RC, Browne PJ, Coombes RC. Separated human breast epithelial and myoepithelial cells have different growth requirements in vitro but can reconstitute normal breast lobuloalveolar structure. J Cell Physiol 1997;171:11–19.

    CAS  PubMed  Google Scholar 

  65. Papini S, Cecchetti D, Campani D, Fitzgerald W, Grivel JC, Chen S, Margolis I, Revoltella RP. Isolation and clonal analysis of human epidermal keratinocyte stem cells in long-term culture. Stem Cells 2003;21:481–94.

    PubMed  Google Scholar 

  66. Sauvageau G, Iscove NN, Humphries RK. in vitro and in vivo expansion of hematopoietic stem cells. Oncogene 2004;23:7223–32.

    CAS  PubMed  Google Scholar 

  67. Sherley JL. Asymmetric cell kinetics genes: the key to expansion of adult stem cells in culture. Stem Cells 2002;20:561–72.

    PubMed  Google Scholar 

  68. Lee HS, Crane GG, Merok JR, Tunstead JR, Hatch NL, Panchalingam K, Powers MJ, Griffith LG, Sherley JL. Clonal expansion of adult rat hepatic stem cell lines by suppression of asymmetric cell kinetics (SACK). Biotech Bioeng 2003;83:760–71.

    CAS  Google Scholar 

  69. Jones PH, Watt FM. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell 1993;73:713–24.

    Article  CAS  PubMed  Google Scholar 

  70. Jones PH, Harper S, Watt FM. Stem cell patterning and fate in human epidermis. Cell 1995;80:83–93.

    CAS  PubMed  Google Scholar 

  71. Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 1992;255:707–10.

    Google Scholar 

  72. Rietze RL, Valcanis H, Brooker GF, Thomas T, Voss AK, Bartlett PF. Purification of a pluripotent neural stem cell from the adult mouse brain. Nature 2001;412:736–39.

    Article  CAS  PubMed  Google Scholar 

  73. Toma JG, Akhaven M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR, Miller FD. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature Cell Biol 2001;3:778–84.

    CAS  PubMed  Google Scholar 

  74. Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL. A role for Wnt signaling in self-renewal of haematopoietic stem cels. Nature 2003;423:409–14.

    CAS  PubMed  Google Scholar 

  75. Ehmann UK, DeVries JT, Chen MS, Adamos AA, Guzman RC, Omary MB. An in vitro model of epithelial cell growth stimulation in the rodent mammary gland. Cell Prolif 2003;36:177–90.

    CAS  PubMed  Google Scholar 

  76. Gudjonsson T, Ronnov-Jessen L, Villadsen R, Rank F, Bissell MJ, Petersen OW. 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 2002;115:39–50.

    CAS  PubMed  Google Scholar 

  77. Hirai Y, Lochter A, Galosy S, Koshida S, Niwa S, Bissell MJ. Epimorphin functions as a key morphoregulator for mammary epithelial cells. J Cell Biol 1998;140:159–69.

    CAS  PubMed  Google Scholar 

  78. Daniel CW, Young LJT, Medina D, DeOme KB. The influence of mammogenic hormones on serially transplanted mouse mammary gland. Exp Gerentol 1971;6:95–101.

    CAS  Google Scholar 

  79. Niranjan B, Buluwela L, Yant J, Perusinghe N, Atherton A, Phippard D, Dale T, Gusterson B, Kamalati T. HGF/SF: A potent cytokine for mammary growth, morphogenesis and development. Development 1995;121:2897–908.

    CAS  PubMed  Google Scholar 

  80. Daniel CW, Silberstein GB, Strickland P. Direct action of 17β-estradiol on mouse mammary ducts analyzed by sustained release implants and steriod autoradiography. Cancer Res 1987;47:6052–57.

    CAS  PubMed  Google Scholar 

  81. Parmar H, Young P, Emerman JT, Neve RM, Dairkee S, Cunha GR. Endocrinology 2002;143:4886–96.

    CAS  PubMed  Google Scholar 

  82. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 2003;100:3983–88.

    Article  CAS  PubMed  Google Scholar 

  83. Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D. Molecular portraits of human breast tumors. Nature 2000;406:747–52.

    CAS  PubMed  Google Scholar 

  84. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Eystein Lonning P, Borresen-Dale AL. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001;98:10869–74.

    CAS  PubMed  Google Scholar 

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Affiliations

  1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

    John Stingl, Afshin Raouf & Connie J. Eaves

  2. StemCell Technologies Inc., Vancouver, British Columbia, Canada

    John Stingl

  3. Department of Anatomy and Cell Biology, University of British Columbia, Vancouver, British Columbia, Canada

    Joanne T. Emerman

  4. The Terry Fox Laboratory, 601 West 10th Avenue, Vancouver, British Columbia, V5Z 1L3, Canada

    Connie J. Eaves

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  1. John Stingl
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  2. Afshin Raouf
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  3. Joanne T. Emerman
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  4. Connie J. Eaves
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Correspondence to Connie J. Eaves.

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Stingl, J., Raouf, A., Emerman, J.T. et al. Epithelial Progenitors in the Normal Human Mammary Gland. J Mammary Gland Biol Neoplasia 10, 49–59 (2005). https://doi.org/10.1007/s10911-005-2540-7

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  • mammary stem cells
  • colony assays
  • flow cytometry
  • cell culture