Journal of the Formosan Medical Association
Volume 107, Issue 10 , Pages 751-766 , October 2008

Breast Cancer Stem Cells and Tumor Suppressor Genes

  • Wendy W. Hwang-Verslues

      Affiliations

    • Genomics Research Center, Academia Sinica, Irvine, California, USA
    • ,
  • King-Jen Chang

      Affiliations

    • Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
    • ,
  • Eva Y.-H.P. Lee

      Affiliations

    • Department of Biological Chemistry, University of California, Irvine, California, USA
    • ,
  • Wen-Hwa Lee

      Affiliations

    • Department of Biological Chemistry, University of California, Irvine, California, USA
    • Corresponding Author InformationCorrespondence to: Dr Wen-Hwa Lee, Department of Biological Chemistry, University of California, Irvine, CA 92697, USA

Received 26 June 2008 ,Revised 9 July 2008 ,Accepted 14 July 2008.

References 

  1. Potten CS , Loeffler M . Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt . Development . 1990;110:1001–1020
  2. Clarke MF , Fuller M . Stem cells and cancer: two faces of eve . Cell . 2006;124:1111–1115
  3. Reya T , Morrison SJ , Clarke MF , et al.   Stem cells, cancer, and cancer stem cells . Nature . 2001;414:105–111
  4. Weissman IL , Anderson DJ , Gage F . Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations . Annu Rev Cell Dev Bio . 2001;17:387–403
  5. Cheng T , Rodrigues N , Dombkowski D , et al.   Stem cell repopulation efficiency but not pool size is governed by p27(kip1) . Nat Med . 2000;6:1235–1240
  6. Cheng T , Rodrigues N , Shen H , et al.   Hematopoietic stem cell quiescence maintained by p21cip1/waf1 . Science . 2000;287:1804–1808
  7. Morrison SJ , Qian D , Jerabek L , et al.   A genetic determinant that specifically regulates the frequency of hematopoietic stem cells . J Immunol . 2002;168:635–642
  8. Passegue E , Wagers AJ , Giuriato S , et al.   Global analysis of proliferation and cell cycle gene expression in the regulation of hematopoietic stem and progenitor cell fates . J Exp Med . 2005;202:1599–1611
  9. Forsberg EC , Prohaska SS , Katzman S , et al.   Differential expression of novel potential regulators in hematopoietic stem cells . PLoS Genet . 2005;1:e28
  10. Spradling A , Drummond-Barbosa D , Kai T . Stem cells find their niche . Nature . 2001;414:98–104
  11. Akala OO , Park IK , Qian D , et al.   Long-term haematopoietic reconstitution by Trp53-/-p16Ink4a-/-p19Arf-/-multipotent progenitors . Nature . 2008;453:228–232
  12. Tan BT , Park CY , Ailles LE , et al.   The cancer stem cell hypothesis: a work in progress . Lab Invest . 2006;86:1203–1207
  13. George AA , Franklin J , Kerkof K , et al.   Detection of leukemic cells in the CD34(+)CD38(−) bone marrow progenitor population in children with acute lymphoblastic leukemia . Blood . 2001;97:3925–3930
  14. Mauro MJ , Druker BJ . Chronic myelogenous leukemia . Curr Opin Oncol . 2001;13:3–7
  15. Miyamoto T , Weissman IL , Akashi K . AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation . Proc Natl Acad Sci USA . 2000;97:7521–7526
  16. Lagasse E , Weissman IL . bcl-2 inhibits apoptosis of neutrophils but not their engulfment by macrophages . J Exp Med . 1994;179:1047–1052
  17. Traver D , Akashi K , Weissman IL , et al.   Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia . Immunity . 1998;9:47–57
  18. Tsai YC , Lu Y , Nichols PW , et al.   Contiguous patches of normal human mammary epithelium derived from a single stem cell: implications for breast carcinogenesis . Cancer Res . 1996;56:402–404
  19. Kordon EC , Smith GH . An entire functional mammary gland may comprise the progeny from a single cell . Development . 1998;125:1921–1930
  20. Shackleton M , Vaillant F , Simpson KJ , et al.   Generation of a functional mammary gland from a single stem cell . Nature . 2006;439:84–88
  21. Stingl J , Eirew P , Ricketson I , et al.   Purification and unique properties of mammary epithelial stem cells . Nature . 2006;439:993–997
  22. Kenney NJ , Smith GH , Lawrence E , et al.   Identification of stem cell units in the terminal end bud and duct of the mouse mammary gland . J Biomed Biotechnol . 2001;1:133–143
  23. Smith GH . Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands . Development . 2005;132:681–687
  24. Hirschmann-Jax C , Foster AE , Wulf GG , et al.   A distinct “side population” of cells with high drug efflux capacity in human tumor cells . Proc Natl Acad Sci USA . 2004;101:14228–14233
  25. Campos LS . Neurospheres: insights into neural stem cell biology . J Neurosci Res . 2004;78:761–769
  26. Kiel MJ , He S , Ashkenazi R , et al.   Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU . Nature . 2007;449:238–242
  27. Morrison SJ , Spradling AC . Stem cells and niches: mechanisms that promote stem cell maintenance throughout life . Cell . 2008;132:598–611
  28. Alvi AJ , Clayton H , Joshi C , et al.   Functional and molecular characterisation of mammary side population cells . Breast Cancer Res . 2003;5:R1–R8
  29. Clarke RB , Anderson E , Howell A , et al.   Regulation of human breast epithelial stem cells . Cell Prolif . 2003;36(Suppl 1):45–58
  30. Clarke RB , Spence K , Anderson E , et al.   A putative human breast stem cell population is enriched for steroid receptorpositive cells . Dev Biol . 2005;277:443–456
  31. Clayton H , Titley I , Vivanco M . Growth and differentiation of progenitor/stem cells derived from the human mammary gland . Exp Cell Res . 2004;297:444–460
  32. Dontu G , Abdallah WM , Foley JM , et al.   In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells . Genes Dev . 2003;17:1253–1270
  33. Dontu G , Wicha MS . Survival of mammary stem cells in suspension culture: implications for stem cell biology and neoplasia . J Mammary Gland Biol Neoplasia . 2005;10:75–86
  34. Bocker W , Moll R , Poremba C , et al.   Common adult stem cells in the human breast give rise to glandular and myoepithelial cell lineages: a new cell biological concept . Lab Invest . 2002;82:737–746
  35. Gudjonsson T , Villadsen R , Nielsen HL , et al.   Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties . Genes Dev . 2002;16:693–706
  36. Stingl J , Raouf A , Eirew P , et al.   Deciphering the mammary epithelial cell hierarchy . Cell Cycle . 2006;5:1519–1522
  37. Welm BE , Tepera SB , Venezia T , et al.   Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population . Dev Biol . 2002;245:42–56
  38. Villadsen R , Fridriksdottir AJ , Ronnov-Jessen L , et al.   Evidence for a stem cell hierarchy in the adult human breast . J Cell Biol . 2007;177:87–101
  39. Bonnet D , Dick JE . Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell . Nat Med . 1997;3:730–737
  40. Al-Hajj M , Wicha MS , Benito-Hernandez A , et al.   Prospective identification of tumorigenic breast cancer cells . Proc Natl Acad Sci USA . 2003;100:3983–3988
  41. Singh SK , Clarke ID , Hide T , et al.   Cancer stem cells in nervous system tumors . Oncogene . 2004;23:7267–7273
  42. Collins AT , Berry PA , Hyde C , et al.   Prospective identification of tumorigenic prostate cancer stem cells . Cancer Res . 2005;65:10946–10951
  43. Fang D , Nguyen TK , Leishear K , et al.   A tumorigenic sub-population with stem cell properties in melanomas . Cancer Res . 2005;65:9328–9337
  44. O'Brien CA , Pollett A , Gallinger S , et al.   A human colon cancer cell capable of initiating tumour growth in immuno-deficient mice . Nature . 2007;445:106–110
  45. Ricci-Vitiani L , Lombardi DG , Pilozzi E , et al.   Identification and expansion of human colon-cancer-initiating cells . Nature . 2007;445:111–115
  46. Matsui W , Huff CA , Wang Q , et al.   Characterization of clonogenic multiple myeloma cells . Blood . 2004;103:2332–2336
  47. Li C , Heidt DG , Dalerba P , et al.   Identification of pancreatic cancer stem cells . Cancer Res . 2007;67:1030–1037
  48. Kim CF , Jackson EL , Woolfenden AE , et al.   Identification of bronchioalveolar stem cells in normal lung and lung cancer . Cell . 2005;121:823–835
  49. Perou CM , Sorlie T , Eisen MB , et al.   Molecular portraits of human breast tumours . Nature . 2000;406:747–752
  50. Sorlie T , Perou CM , Tibshirani R , et al.   Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications . Proc Natl Acad Sci USA . 2001;98:10869–10874
  51. Sorlie T , Tibshirani R , Parker J , et al.   Repeated observation of breast tumor subtypes in independent gene expression data sets . Proc Natl Acad Sci USA . 2003;100:8418–8423
  52. Sotiriou C , Neo SY , McShane LM , et al.   Breast cancer classification and prognosis based on gene expression profiles from a population-based study . Proc Natl Acad Sci USA . 2003;100:10393–10398
  53. Stingl J , Caldas C . Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis . Nat Rev Cancer . 2007;7:791–799
  54. Vargo-Gogola T , Rosen JM . Modelling breast cancer: one size does not fit all . Nat Rev Cancer . 2007;7:659–672
  55. Ponti D , Costa A , Zaffaroni N , et al.   Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties . Cancer Res . 2005;65:5506–5511
  56. Dontu G , Jackson KW , McNicholas E , et al.   Role of Notch signaling in cell-fate determination of human mammary stem/progenitor cells . Breast Cancer Res . 2004;6:R605–R615
  57. Liu S , Dontu G , Mantle ID , et al.   Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells . Cancer Res . 2006;66:6063–6071
  58. Sansone P , Storci G , Giovannini C , et al.   p66Shc/Notch-3 interplay controls self-renewal and hypoxia survival in human stem/progenitor cells of the mammary gland expanded in vitro as mammospheres . Stem Cells . 2007;25:807–815
  59. Shipitsin M , Campbell LL , Argani P , et al.   Molecular definition of breast tumor heterogeneity . Cancer Cell . 2007;11:259–273
  60. Storci G , Sansone P , Trere D , et al.   The basal-like breast carcinoma phenotype is regulated by SLUG gene expression . J Pathol . 2008;214:25–37
  61. Yu F , Yao H , Zhu P , et al.   Let-7 regulates self renewal and tumorigenicity of breast cancer cells . Cell . 2007;131:1109–1123
  62. Zhou J , Wulfkuhle J , Zhang H , et al.   Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance . Proc Natl Acad Sci USA . 2007;104:16158–16163
  63. Ginestier C , Hur MH , Charafe-Jauffret E , et al.   ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome . Cell Stem Cell . 2007;1:555–567
  64. Wright MH , Calcagno AM , Salcido CD , et al.   Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics . Breast Cancer Res . 2008;10:R10
  65. Ivanova NB , Dimos JT , Schaniel C , et al.   A stem cell molecular signature . Science . 2002;298:601–604
  66. Vercauteren SM , Sutherland HJ . CD133 (AC133) expression on AML cells and progenitors . Cytotherapy . 2001;3:449–459
  67. Yin S , Li J , Hu C , et al.   CD133 positive hepatocellular carcinoma cells possess high capacity for tumorigenicity . Int J Cancer . 2007;120:1444–1450
  68. Cariati M , Naderi A , Brown JP , et al.   Alpha-6 integrin is necessary for the tumourigenicity of a stem cell-like sub-population within the MCF7 breast cancer cell line . Int J Cancer . 2008;122:298–304
  69. Fillmore CM , Kuperwasser C . Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy . Breast Cancer Res . 2008;10:R25
  70. Hughes L , Malone C , Chumsri S , et al.   Characterisation of breast cancer cell lines and establishment of a novel isogenic subclone to study migration, invasion and tumourigenicity . Clin Exp Metastasis . 2008;25:549–557
  71. Phillips TM , McBride WH , Pajonk F . The response of CD24(-/low)/CD44 + breast cancer-initiating cells to radiation . J Natl Cancer Inst . 2006;98:1777–1785
  72. Sheridan C , Kishimoto H , Fuchs RK , et al.   CD44+/CD24-breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis . Breast Cancer Res . 2006;8:R59
  73. Tang B , Yoo N , Vu M , et al.   Transforming growth factor-beta can suppress tumorigenesis through effects on the putative cancer stem or early progenitor cell and committed progeny in a breast cancer xenograft model . Cancer Res . 2007;67:8643–8652
  74. Woodward WA , Chen MS , Behbod F , et al.   WNT/beta-catenin mediates radiation resistance of mouse mammary progenitor cells . Proc Natl Acad Sci USA . 2007;104:618–623
  75. Lee WH . The molecular basis of cancer suppression by the retinoblastoma gene . Princess Takamatsu Symp . 1989;20:159–170
  76. Bosco EE , Knudsen ES . RB in breast cancer: at the cross-roads of tumorigenesis and treatment . Cell Cycle . 2007;6:667–671
  77. Antoniou AC , Easton DF . Models of genetic susceptibility to breast cancer . Oncogene . 2006;25:5898–5905
  78. Walsh T , King MC . Ten genes for inherited breast cancer . Cancer Cell . 2007;11:103–105
  79. Reya T , Clevers H . Wnt signalling in stem cells and cancer . Nature . 2005;434:843–850
  80. Reya T , Duncan AW , Ailles L , et al.   A role for Wnt signalling in self-renewal of haematopoietic stem cells . Nature . 2003;423:409–414
  81. Huang HJ , Yee JK , Shew JY , et al.   Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells . Science . 1988;242:1563–1566
  82. Riley DJ , Lee EY , Lee WH . The retinoblastoma protein: more than a tumor suppressor . Annu Rev Cell Biol . 1994;10:1–29
  83. Frolov MV , Dyson NJ . Molecular mechanisms of E2F-dependent activation and pRB-mediated repression . J Cell Sci . 2004;117:2173–2181
  84. Jackson MW , Agarwal MK , Yang J , et al.   p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2 . J Cell Sci . 2005;118:1821–1832
  85. Zheng L , Lee WH . The retinoblastoma gene: a prototypic and multifunctional tumor suppressor . Exp Cell Res . 2001;264:2–18
  86. van Deursen JM . Rb loss causes cancer by driving mitosis mad . Cancer Cell . 2007;11:1–3
  87. Zheng L , Flesken-Nikitin A , Chen PL , et al.   Deficiency of retinoblastoma gene in mouse embryonic stem cells leads to genetic instability . Cancer Res . 2002;62:2498–2502
  88. Skapek SX , Pan YR , Lee EY . Regulation of cell lineage specification by the retinoblastoma tumor suppressor . Oncogene . 2006;25:5268–5276
  89. Borg A , Zhang QX , Alm P , et al.   The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression . Cancer Res . 1992;52:2991–2994
  90. Chano T , Kontani K , Teramoto K , et al.   Truncating mutations of RB1CC1 in human breast cancer . Nat Genet . 2002;31:285–288
  91. Oesterreich S , Fuqua SA . Tumor suppressor genes in breast cancer . Endocr Relat Cancer . 1999;6:405–419
  92. Pietilainen T , Lipponen P , Aaltomaa S , et al.   Expression of retinoblastoma gene protein (Rb) in breast cancer as related to established prognostic factors and survival . Eur J Cancer . 1995;31A:329–333
  93. Bosco EE , Wang Y , Xu H , et al.   The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer . J Clin Invest . 2007;117:218–228
  94. Jares P , Rey MJ , Fernandez PL , et al.   Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status . J Pathol . 1997;182:160–166
  95. Nielsen NH , Loden M , Cajander J , et al.   G1-S transition defects occur in most breast cancers and predict outcome . Breast Cancer Res Treat . 1999;56:105–112
  96. Eeckhoute J , Carroll JS , Geistlinger TR , et al.   A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer . Genes Dev . 2006;20:2513–2526
  97. Foster JS , Henley DC , Ahamed S , et al.   Estrogens and cell-cycle regulation in breast cancer . Trends Endocrinol Metab . 2001;12:320–327
  98. Osborne CK , Boldt DH , Clark GM , et al.   Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase . Cancer Res . 1983;43:3583–3585
  99. Watts CK , Brady A , Sarcevic B , et al.   Antiestrogen inhibition of cell cycle progression in breast cancer cells in associated with inhibition of cyclin-dependent kinase activity and decreased retinoblastoma protein phospho-rylation . Mol Endocrinol . 1995;9:1804–1813
  100. Mullan PB , Quinn JE , Harkin DP . The role of BRCA1 in transcriptional regulation and cell cycle control . Oncogene . 2006;25:5854–5863
  101. Aprelikova ON , Fang BS , Meissner EG , et al.   BRCA1-associated growth arrest is RB-dependent . Proc Natl Acad Sci USA . 1999;96:11866–11871
  102. Ting NS , Lee WH . The DNA double-strand break response pathway: becoming more BRCAish than ever . DNA Repair (Amst) . 2004;3:935–944
  103. Turner N , Tutt A , Ashworth A . Hallmarks of ‘BRCAness’ in sporadic cancers . Nat Rev Cancer . 2004;4:814–819
  104. Heine GF , Parvin JD . BRCA1 control of steroid receptor ubiquitination . Sci STKE . 2007;391:pe34
  105. Esteller M , Silva JM , Dominguez G , et al.   Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors . J Natl Cancer Inst . 2000;92:564–569
  106. Turner NC , Reis-Filho JS . Basal-like breast cancer and the BRCA1 phenotype . Oncogene . 2006;25:5846–5853
  107. Saal LH , Gruvberger-Saal SK , Persson C , et al.   Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair . Nat Genet . 2008;40:102–107
  108. Bradley A , Medina D . Introduction: BRCA1 and BRCA2 in mammary gland development and tumorigenesis . J Mammary Gland Biol Neoplasia . 1998;3:363–364
  109. Furuta S , Jiang X , Gu B , et al.   Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary epithelial cells . Proc Natl Acad Sci USA . 2005;102:9176–9181
  110. Kubista M , Rosner M , Miloloza A , et al.   Brca1 and differentiation . Mutat Res . 2002;512:165–172
  111. Liu S , Ginestier C , Charafe-Jauffret E , et al.   BRCA1 regulates human mammary stem/progenitor cell fate . Proc Natl Acad Sci USA . 2008;105:1680–1685
  112. Farmer H , McCabe N , Lord CJ , et al.   Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy . Nature . 2005;434:917–921
  113. Bhattacharyya A , Ear US , Koller BH , et al.   The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin . J Biol Chem . 2000;275:23899–23903
  114. Tassone P , Tagliaferri P , Perricelli A , et al.   BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells . Br J Cancer . 2003;88:1285–1291
  115. Poole AJ , Li Y , Kim Y , et al.   Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist . Science . 2006;314:1467–1470
  116. Shafee N , Smith CR , Wei S , et al.   Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors . Cancer Res . 2008;68:3243–3250
  117. Daniels MJ , Wang Y , Lee M , et al.   Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2 . Science . 2004;306:876–879
  118. Nathanson KL , Wooster R , Weber BL . Breast cancer genetics: what we know and what we need . Nat Med . 2001;7:552–556
  119. Powell SN , Kachnic LA . Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation . Oncogene . 2003;22:5784–5791
  120. Shamoo Y . Structural insights into BRCA2 function . Curr Opin Struct Biol . 2003;13:206–211
  121. Walsh T , Casadei S , Coats KH , et al.   Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer . JAMA . 2006;295:1379–1388
  122. Mathew CG . Fanconi anaemia genes and susceptibility to cancer . Oncogene . 2006;25:5875–5884
  123. Edwards SL , Brough R , Lord CJ , et al.   Resistance to therapy caused by intragenic deletion in BRCA2 . Nature . 2008;451:1111–1115
  124. Sakai W , Swisher EM , Karlan BY , et al.   Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers . Nature . 2008;451:1116–1120
  125. Lacroix M , Toillon RA , Leclercq G . p53 and breast cancer, an update . Endocr Relat Cancer . 2006;13:293–325
  126. Vogelstein B , Lane D , Levine AJ . Surfing the p53 network . Nature . 2000;408:307–310
  127. Vousden KH , Lu X . Live or let die: the cell's response to p53 . Nat Rev Cancer . 2002;2:594–604
  128. Zhao R , Gish K , Murphy M , et al.   Analysis of p53-regulated gene expression patterns using oligonucleotide arrays . Genes Dev . 2000;14:981–993
  129. Bargonetti J , Manfredi JJ . Multiple roles of the tumor suppressor p53 . Curr Opin Oncol . 2002;14:86–91
  130. Sigal A , Rotter V . Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome . Cancer Res . 2000;60:6788–6793
  131. Ko LJ , Prives C . p53: puzzle and paradigm . Genes Dev . 1996;10:1054–1072
  132. Foray N , Marot D , Gabriel A , et al.   A subset of ATM- and ATR-dependent phosphorylation events requires the BRCA1 protein . EMBO J . 2003;22:2860–2871
  133. Hohenstein P , Giles RH . BRCA1: a scaffold for p53 response? . Trends Genet . 2003;19:489–494
  134. Crook T , Crossland S , Crompton MR , et al.   p53 mutations in BRCA1-associated familial breast cancer . Lancet . 1997;350:638–639
  135. Borresen-Dale AL . TP53 and breast cancer . Hum Mutat . 2003;21:292–300
  136. Meletis K , Wirta V , Hede SM , et al.   p53 suppresses the self-renewal of adult neural stem cells . Development . 2006;133:363–439

PII: S0929-6646(08)60188-6

doi: 10.1016/S0929-6646(08)60188-6

Journal of the Formosan Medical Association
Volume 107, Issue 10 , Pages 751-766 , October 2008

Article Tools