What Can We Learn about Breast Cancer from Stem Cells?

  • Michael F. Clarke
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

To survive into adulthood, long-lived organisms such as man need to maintain the many diverse organs and tissues that are necessary for the myriads of essential functions such as absorption of nutrients, protection from infection, and replacement of cells damaged by insults including toxins, radiation and trauma. This need to constantly replenish the mature cells of a tissue presents a particularly vexing problem for complex multicellular animals. Cells must be able to replicate in order to replace the old or damaged cells, but this replication must be tightly regulated to prevent the accumulation of errors that result in the development of tumors and eventually cancer (1,2).


Stem Cell Embryonic Stem Cell Cancer Stem Cell Human Embryonic Stem Cell Leukemic Stem Cell 
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.


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  1. 1.
    Clarke MF, Fuller M (2006) Stem cells and cancer: two faces of eve. Cell 124:1111–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767.PubMedCrossRefGoogle Scholar
  3. 3.
    Smith GH, Chepko G (2001) Mammary epithelial stem cells. Microsc Res Tech 52:190–203.PubMedCrossRefGoogle Scholar
  4. 4.
    Blanpain C, Lowry WE, Geoghegan A, et al. (2004) Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118:635–48.PubMedCrossRefGoogle Scholar
  5. 5.
    Nilsson E, Parrott JA, Skinner MK (2001) Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol 175:123–30.PubMedCrossRefGoogle Scholar
  6. 6.
    Vasioukhin V, Bauer C, Degenstein L, et al. (2001) Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell 104:605–17.PubMedCrossRefGoogle Scholar
  7. 7.
    Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62.PubMedCrossRefGoogle Scholar
  8. 8.
    Blyszczuk P (2004) Embryonic stem cells differentiate into insulin-producing cells without selection of nestin-expressing cells. Int J Dev Biol 48:1095–104.PubMedCrossRefGoogle Scholar
  9. 9.
    Bouwens L, De Blay E (1996) Islet morphogenesis and stem cell markers in rat pancreas. J Histochem Cytochem 44:947–51.PubMedGoogle Scholar
  10. 10.
    Doetsch F, Petreanu L, Caille I, et al. (2002) EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells. Neuron 36:1021–34.PubMedCrossRefGoogle Scholar
  11. 11.
    Chepko G, Smith GH (1999) Mammary epithelial stem cells: our current understanding. J Mammary Gland Biol Neoplasia 4:35–52.PubMedCrossRefGoogle Scholar
  12. 12.
    Easterday MC (2003) Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations. Dev Biol 264:309–22.PubMedCrossRefGoogle Scholar
  13. 13.
    Taipale J, Beachy PA (2001) The Hedgehog and Wnt signalling pathways in cancer. Nature 411:349–54.PubMedCrossRefGoogle Scholar
  14. 14.
    van Es JH (2005) Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435:959–63.PubMedCrossRefGoogle Scholar
  15. 15.
    Chan EF, Gat U, McNiff JM, Fuchs EA (1999) Common human skin tumour is caused by activating mutations in beta-catenin. Nat Genet 21:410–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Shackleton M (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Morrison SJ, et al. (2002) A genetic determinant that specifically regulates the frequency of hematopoietic stem cells. J Immunol 168:635–42.PubMedGoogle Scholar
  18. 18.
    Allman D, Aster JC, Pear WS (2002) Notch signaling in hematopoiesis and early lymphocyte development. Immunol Rev 187:75–86.PubMedCrossRefGoogle Scholar
  19. 19.
    Beachy PA, Karhadkar SS, Berman DM (2004) Tissue repair and stem cell renewal in carcinogenesis. Nature 432:324–31.PubMedCrossRefGoogle Scholar
  20. 20.
    Boyer LA, et al. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–56.PubMedCrossRefGoogle Scholar
  21. 21.
    Cavaleri F, Scholer HR (2003) Nanog: a new recruit to the embryonic stem cell orchestra. Cell 113:551–2.PubMedCrossRefGoogle Scholar
  22. 22.
    Ema H, Takano H, Sudo K, Nakauchi H (2000) In vitro self-renewal division of hematopoietic stem cells. J Exp Med 192:1281–8.PubMedCrossRefGoogle Scholar
  23. 23.
    He XC, et al. (2004) BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-beta-catenin signaling. Nat Genet 36:1117–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Hitoshi S, et al. (2002) Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev 16:846–58.PubMedCrossRefGoogle Scholar
  25. 25.
    Huntly BJ, et al. (2004) MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6:587–96.PubMedCrossRefGoogle Scholar
  26. 26.
    Kyba M, Perlingeiro RC, Daley GQ (2002) HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell 109, 29–37.PubMedCrossRefGoogle Scholar
  27. 27.
    Loh YH, et al. (2006) The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 38:431–40.PubMedCrossRefGoogle Scholar
  28. 28.
    Mitsui K, et al. (2003) The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell 113:631–42.PubMedCrossRefGoogle Scholar
  29. 29.
    Molofsky AV, et al. (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425:962–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Morrison SJ, et al. (2000) Transient notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 101:499–510.PubMedCrossRefGoogle Scholar
  31. 31.
    Nakamura Y, et al. (2000) The bHLH gene hes1 as a repressor of the neuronal commitment of CNS stem cells. J Neurosci 20:283–93.PubMedGoogle Scholar
  32. 32.
    Ohta H, et al. (2002) Polycomb group gene rae28 is required for sustaining activity of hematopoietic stem cells. J Exp Med 195:759–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Park IK, et al. (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Reya T, et al. (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–14.PubMedCrossRefGoogle Scholar
  35. 35.
    Xu RH, et al. (2005) Basic FGF and suppression of BMP signaling sustain undifferentiated proliferation of human ES cells. Nat Meth 2:185–90.CrossRefGoogle Scholar
  36. 36.
    Ying QL, Nichols J, Chambers I, Smith A (2003) BMP induction of Id proteins suppresses differentiation and sustains embryonic stem cell self-renewal in collaboration with STAT3. Cell 115:281–92.PubMedCrossRefGoogle Scholar
  37. 37.
    Zaehres H, et al. (2005) High-efficiency RNA interference in human embryonic stem cells. Stem Cells 23:299–305.PubMedCrossRefGoogle Scholar
  38. 38.
    Liang SH, Clarke MF (2001) Regulation of p53 localization. Eur J Biochem 268:2779–83.PubMedCrossRefGoogle Scholar
  39. 39.
    Krishnamurthy J, et al. (2006) p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443:453–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Molofsky AV, et al. (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443:448–52.PubMedCrossRefGoogle Scholar
  41. 41.
    Janzen V, et al. (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443:421–6.PubMedGoogle Scholar
  42. 42.
    Lee TI, et al. (2006) Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125:301–13.PubMedCrossRefGoogle Scholar
  43. 43.
    Akala OO, Clarke MF (2006) Hematopoietic stem cell self-renewal. Curr Opin Genet Dev 16:496–501.PubMedCrossRefGoogle Scholar
  44. 44.
    Reya T, Morrison SJ, Clarke MF, Weissman IL (2001) Stem cells, cancer, and cancer stem cells. Nature 414:105–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–8.PubMedCrossRefGoogle Scholar
  46. 46.
    Clarke MF (2004) Neurobiology: at the root of brain cancer. Nature 432:281–2.PubMedCrossRefGoogle Scholar
  47. 47.
    Fang D, et al. (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328–37.PubMedCrossRefGoogle Scholar
  48. 48.
    Singh SK, et al. (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–8.PubMedGoogle Scholar
  49. 49.
    Liu R, et al. (2007) The prognastic role of a gene signature from tumorigenic breast-cancers cells. N Engl J Med 356:217–26.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Michael F. Clarke
    • 1
  1. 1.Deputy Director of the Stem and Regenerative Medicine InstStanford UniversityPalo AltoUSA

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