Gastrointestinal stem cells in self-renewal and cancer

Journal of Gastroenterology

Volumn 46, Issue 9, 2011, Pages 1039-1055

  Lin, S Adelia ^a   Barker, Nick ^a  

^a INSTITUTE OF MEDICAL BIOLOGY   (Singapore)

Author keywords

Cancer; Intestine; Self renewal; Stem cell; Stomach

Indexed keywords

BIOLOGICAL MARKER; BMI1 PROTEIN; CD133 ANTIGEN; CELL DNA; MEMBRANE PROTEIN; MUSASHI 1; PROMININ1; PROTEIN ASCL2; PROTEIN DCAMKL1; PROTEIN LGR5; PROTEIN MTERT; PROTEIN OLFM4; TRANSCRIPTION FACTOR SOX9; UNCLASSIFIED DRUG; VILLIN;

CANCER STEM CELL; CELL FUNCTION; CELL ISOLATION; CELL LABELING; CELL LINEAGE; CELL POPULATION; CELL RENEWAL; DIGESTIVE SYSTEM CANCER; GASTROINTESTINAL STEM CELL; HOMEOSTASIS; HUMAN; INTESTINE EPITHELIUM; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN TARGETING; REVIEW; STEM CELL TRANSPLANTATION;

ANIMALS; ANTIBODIES; BIOLOGICAL MARKERS; GASTROINTESTINAL NEOPLASMS; GASTROINTESTINAL TRACT; HUMANS; INTESTINAL MUCOSA; MICE; NEOPLASTIC STEM CELLS; STEM CELLS;

EID: 80755133637     PISSN: 09441174     EISSN: 14355922     Source Type: Journal    
DOI: 10.1007/s00535-011-0424-8     Document Type: Review

References (111)

1. Snippert HJ, van der Flier LG, Sato T, van Es JH, van den Born M, Kroon-Veenboer C, et al. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell. 2010;143:134-44.
2. Fuchs E. The tortoise and the hair: slow-cycling cells in the stem cell race. Cell. 2009;137:811-9.
3. Tumbar T, Guasch G, Greco V, Blanpain C, Lowry WE, Rendl M, et al. Defining the epithelial stem cell niche in skin. Science. 2004;303:359-63. (Pubitemid 38095773)
4. Lobo NA, Shimono Y, Qian D, Clarke MF. The biology of cancer stem cells. Annu Rev Cell Dev Biol. 2007;23:675-99.
5. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007;449:1003-7. (Pubitemid 350014593)
6. Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, et al. Lgr5(?ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell. 2010;6:25-36.
7. Jaks V, Barker N, Kasper M, van Es JH, Snippert HJ, Clevers H, et al. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet. 2008;40:1291-9.
8. Klein AM, Nakagawa T, Ichikawa R, Yoshida S, Simons BD. Mouse germ line stem cells undergo rapid and stochastic turnover. Cell Stem Cell. 2010;7:214-24.
9. Marshman E, Booth C, Potten CS. The intestinal epithelial stem cell. Bioessays. 2002;24:91-8. (Pubitemid 34108424)
10. Bjerknes M, Cheng H. Intestinal epithelial stem cells and progenitors. Methods Enzymol. 2006;419:337-83. (Pubitemid 44820373)
11. van der Flier LG, Clevers H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol. 2009;71:241-60.
12. Casali A, Batlle E. Intestinal stem cells in mammals and Drosophila. Cell Stem Cell. 2009;4:124-7.
13. Vries RG, Huch M, Clevers H. Stem cells and cancer of the stomach and intestine. Mol Oncol. 2010;4:373-84.
14. Barker N, Bartfeld S, Clevers H. Tissue-resident adult stem cell populations of rapidly self-renewing organs. Cell Stem Cell. 2010;7:656-70.
15. Nabeyama A, Leblond CP. "Caveolated cells" characterized by deep surface invaginations and abundant filaments in mouse gastro-intestinal epithelia. Am J Anat. 1974;140:147-65.
16. Gerbe F, van Es JH, Makrini L, Brulin B, Mellitzer G, Robine S, et al. Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. J Cell Biol. 2011;192:767-80.
17. Madara JL, Neutra MR, Trier JS. Junctional complexes in fetal rat small intestine during morphogenesis. Dev Biol. 1981;86:170-8. (Pubitemid 11021753)
18. Bjerknes M, Cheng H. Clonal analysis of mouse intestinal epithelial progenitors. Gastroenterology. 1999;116:7-14. (Pubitemid 29013487)
19. Cairnie AB, Lamerton LF, Steel GG. Cell proliferation studies in the intestinal epithelium of the rat. I. Determination of the kinetic parameters. Exp Cell Res. 1965;39:528-38.
20. Potten CS, Kovacs L, Hamilton E. Continuous labelling studies on mouse skin and intestine. Cell Tissue Kinet. 1974;7:271-83.
21. Potten CS. Extreme sensitivity of some intestinal crypt cells to X and gamma irradiation. Nature. 1977;269:518-21. (Pubitemid 8245145)
22. Potten CS, Owen G, Booth D. Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci. 2002;115:2381-8. (Pubitemid 34752981)
23. Cheng H, Leblond CP. Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian theory of the origin of the four epithelial cell types. Am J Anat. 1974;141:537-61.
24. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med. 1996;183:1797-806. (Pubitemid 26134320)
25. Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G, et al. Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species. Nat Med. 1997;3:1337-45. (Pubitemid 28011033)
26. Challen GA, Little MH. A side order of stem cells: the SP phenotype. Stem Cells. 2006;24:3-12.
27. Bonfanti P, Claudinot S, Amici AW, Farley A, Blackburn CC, Barrandon Y. Microenvironmental reprogramming of thymic epithelial cells to skin multipotent stem cells. Nature. 2010;466: 978-82.
28. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, Li S, et al. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol. 2004;22:411-7. (Pubitemid 38451371)
29. Van der Flier LG, Sabates-Bellver J, Oving I, Haegebarth A, De Palo M, Anti M, et al. The intestinal Wnt/TCF signature. Gastroenterology. 2007;132:628-32.
30. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459:262-5.
31. Sangiorgi E, Capecchi MR. Bmi1 is expressed in vivo in intestinal stem cells. Nat Genet. 2008;40:915-20. (Pubitemid 351913652)
32. Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ. Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature. 2003;425: 962-7. (Pubitemid 37376927)
33. Yadirgi G, Leinster VH, Acquati S, Bhagat H, Shakhova O, Marino S. Conditional activation of Bmi1 expression regulates self renewal, apoptosis and differentiation of neural stem/progenitor cells in vitro and in vivo. Stem Cells. 2011;29(4):700-12.
34. Chatoo W, Abdouh M, Duparc RH, Bernier G. Bmi1 distinguishes immature retinal progenitor/stem cells from the main progenitor cell population and is required for normal retinal development. Stem Cells. 2010;28:1412-23.
35. Konuma T, Oguro H, Iwama A. Role of the polycomb group proteins in hematopoietic stem cells. Dev Growth Differ. 2010;52:505-16.
36. van der Flier LG, van Gijn ME, Hatzis P, Kujala P, Haegebarth A, Stange DE, et al. Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell. 2009;136:903-12.
37. Weigmann A, Corbeil D, Hellwig A, Huttner WB. Prominin, a novel microvilli-specific polytopic membrane protein of the apical surface of epithelial cells, is targeted to plasmalemmal protrusions of non-epithelial cells. Proc Natl Acad Sci USA. 1997;94:12425-30.
38. Miraglia S, Godfrey W, Yin AH, Atkins K, Warnke R, Holden JT, et al. A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning. Blood. 1997;90:5013-21. (Pubitemid 28007218)
39. Lindgren D, Bostrom AK, Nilsson K, Hansson J, Sjolund J, Moller C, et al. Isolation and characterization of progenitor-like cells from human renal proximal tubules. Am J Pathol. 2011;178:828-37.
40. Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT. CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci. 2004;117:3539-45. (Pubitemid 39206394)
41. Zhu L, Gibson P, Currle DS, Tong Y, Richardson RJ, Bayazitov IT, et al. Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature. 2009;457:603-7.
42. Snippert HJ, van Es JH, van den Born M, Begthel H, Stange DE, Barker N, et al. Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology 2009;136:2187-2194.e1.
43. Breault DT, Min IM, Carlone DL, Farilla LG, Ambruzs DM, Henderson DE, et al. Generation of mTert-GFP mice as a model to identify and study tissue progenitor cells. Proc Natl Acad Sci USA. 2008;105:10420-5.
44. Montgomery RK, Carlone DL, Richmond CA, Farilla L, Kranendonk ME, Henderson DE, et al. Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc Natl Acad Sci USA. 2011;108:179-84.
45. Schepers AG, Vries R, van den Born M, van de Wetering M, Clevers H. Lgr5 intestinal stem cells have high telomerase activity and randomly segregate their chromosomes. EMBO J. 2011;30:1104-9.
46. Van Der Flier LG, Haegebarth A, Stange DE, van de Wetering M, Clevers H. OLFM4 is a robust marker for stem cells in human intestine and marks a subset of colorectal cancer cells. Gastroenterology. 2009;137:15-7.
47. Johnson JE, Birren SJ, Anderson DJ. Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors. Nature. 1990;346:858-61.
48. Blache P, van de Wetering M, Duluc I, Domon C, Berta P, Freund JN, et al. SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes. J Cell Biol. 2004;166:37-47. (Pubitemid 38931915)
49. Formeister EJ, Sionas AL, Lorance DK, Barkley CL, Lee GH, Magness ST. Distinct SOX9 levels differentially mark stem/ progenitor populations and enteroendocrine cells of the small intestine epithelium. Am J Physiol Gastrointest Liver Physiol. 2009;296:G1108-18.
50. Gracz AD, Ramalingam S, Magness ST. Sox9 expression marks a subset of CD24-expressing small intestine epithelial stem cells that form organoids in vitro. Am J Physiol Gastrointest Liver Physiol. 2010;298:G590-600.
51. Mori-Akiyama Y, van den Born M, van Es JH, Hamilton SR, Adams HP, Zhang J, et al. SOX9 is required for the differentiation of Paneth cells in the intestinal epithelium. Gastroenterology. 2007;133:539-46. (Pubitemid 47187347)
52. Okano H, Imai T, Okabe M. Musashi: a translational regulator of cell fate. J Cell Sci. 2002;115:1355-9. (Pubitemid 34428693)
53. Kawahara H, Imai T, Imataka H, Tsujimoto M, Matsumoto K, Okano H. Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP. J Cell Biol. 2008;181:639-53. (Pubitemid 351717511)
54. Nakamura M, Okano H, Blendy JA, Montell C. Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. Neuron. 1994;13:67-81. (Pubitemid 24238415)
55. Sakakibara S, Imai T, Hamaguchi K, Okabe M, Aruga J, Nakajima K, et al. Mouse-Musashi-1, a neural RNA-binding protein highly enriched in the mammalian CNS stem cell. Dev Biol. 1996;176:230-42. (Pubitemid 26202815)
56. Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T. Function of RNA-binding protein Musashi-1 in stem cells. Exp Cell Res. 2005;306:349-56. (Pubitemid 40732760)
57. Potten CS, Booth C, Tudor GL, Booth D, Brady G, Hurley P, et al. Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation. 2003;71:28-41. (Pubitemid 38230417)
58. Kayahara T, Sawada M, Takaishi S, Fukui H, Seno H, Fukuzawa H, et al. Candidate markers for stem and early progenitor cells, Musashi-1 and Hes1, are expressed in crypt base columnar cells of mouse small intestine. FEBS Lett. 2003;535:131-5. (Pubitemid 36126368)
59. He XC, Yin T, Grindley JC, Tian Q, Sato T, Tao WA, et al. PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet. 2007;39:189-98. (Pubitemid 46184349)
60. Rezza A, Skah S, Roche C, Nadjar J, Samarut J, Plateroti M. The overexpression of the putative gut stem cell marker Musashi- 1 induces tumorigenesis through Wnt and Notch activation. J Cell Sci. 2010;123:3256-65.
61. Lin PT, Gleeson JG, Corbo JC, Flanagan L, Walsh CA. DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization. J Neurosci. 2000;20:9152-61. (Pubitemid 32042918)
62. Giannakis M, Stappenbeck TS, Mills JC, Leip DG, Lovett M, Clifton SW, et al. Molecular properties of adult mouse gastric and intestinal epithelial progenitors in their niches. J Biol Chem. 2006;281:11292-300.
63. May R, Riehl TE, Hunt C, Sureban SM, Anant S, Houchen CW. Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/ multiple intestinal neoplasia mice. Stem Cells. 2008;26:630-7.
64. Gerbe F, Brulin B, Makrini L, Legraverend C, Jay P. DCAMKL- 1 expression identifies Tuft cells rather than stem cells in the adult mouse intestinal epithelium. Gastroenterology 2009;137:2179-80 (author reply 2180-1).
65. Lim SC. CD24 and human carcinoma: tumor biological aspects. Biomed Pharmacother. 2005;59(Suppl 2):S351-4.
66. von Furstenberg RJ, Gulati AS, Baxi A, Doherty JM, Stappenbeck TS, Gracz AD, et al. Sorting mouse jejunal epithelial cells with CD24 yields a population with characteristics of intestinal stem cells. Am J Physiol Gastrointest Liver Physiol. 2011;300: G409-17.
67. Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature. 2011;469:415-8.
68. Radtke F, Clevers H. Self-renewal and cancer of the gut: two sides of a coin. Science. 2005;307:1904-9.
69. Korinek V, Barker N, Moerer P, van Donselaar E, Huls G, Peters PJ, et al. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet. 1998;19:379-83. (Pubitemid 28357912)
70. Neumuller RA, Knoblich JA. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev. 2009;23:2675-99.
71. Lopez-Garcia C, Klein AM, Simons BD, Winton DJ. Intestinal stem cell replacement follows a pattern of neutral drift. Science. 2010;330:822-5.
72. Cairns J. Mutation selection and the natural history of cancer. Nature. 1975;255:197-200.
73. Quyn AJ, Appleton PL, Carey FA, Steele RJ, Barker N, Clevers H, et al. Spindle orientation bias in gut epithelial stem cell compartments is lost in precancerous tissue. Cell Stem Cell. 2010;6:175-81.
74. Lee ER, Trasler J, Dwivedi S, Leblond CP. Division of the mouse gastric mucosa into zymogenic and mucous regions on the basis of gland features. Am J Anat. 1982;164:187-207. (Pubitemid 12099299)
75. Nomura S, Esumi H, Job C, Tan SS. Lineage and clonal development of gastric glands. Dev Biol. 1998;204:124-35. (Pubitemid 28563869)
76. Karam SM, Leblond CP. Identifying and counting epithelial cell types in the "corpus" of the mouse stomach. Anat Rec. 1992;232:231-46.
77. Lee ER, Leblond CP. Dynamic histology of the antral epithelium in the mouse stomach: IV. Ultrastructure and renewal of gland cells. Am J Anat. 1985;172:241-59. (Pubitemid 15149013)
78. Lee ER, Leblond CP. Dynamic histology of the antral epithelium in the mouse stomach: II. Ultrastructure and renewal of isthmal cells. Am J Anat. 1985;172:205-24. (Pubitemid 15149011)
79. Bjerknes M, Cheng H. Multipotential stem cells in adult mouse gastric epithelium. Am J Physiol Gastrointest Liver Physiol. 2002;283:G767-77.
80. Stevens CE, Leblond CP. Renewal of the mucous cells in the gastric mucosa of the rat. Anat Rec. 1953;115:231-45.
81. Karam SM, Leblond CP. Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anat Rec. 1993;236:259-79. (Pubitemid 23148418)
82. Qiao XT, Ziel JW, McKimpson W, Madison BB, Todisco A, Merchant JL, et al. Prospective identification of a multilineage progenitor in murine stomach epithelium. Gastroenterology. 2007;133:1989-98.
83. Quante M, Marrache F, Goldenring JR, Wang TC. TFF2 mRNA transcript expression marks a gland progenitor cell of the gastric oxyntic mucosa. Gastroenterology 2010;139:2018-2027.e2.
84. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861-72. (Pubitemid 350138099)
85. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917-20.
86. Hamburger AW, Salmon SE. Primary bioassay of human tumor stem cells. Science. 1977;197:461-3.
87. Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755-68.
88. Clevers H. The cancer stem cell: premises, promises and challenges. Nat Med. 2011;17:313-9.
89. Visvader JE. Cells of origin in cancer. Nature. 2011;469:314-22.
90. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres- Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645-8. (Pubitemid 24067706)
91. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3:730-7. (Pubitemid 27298715)
92. 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;100:3983-8. (Pubitemid 36418143)
93. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445:106-10. (Pubitemid 46067310)
94. Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, et al. Identification and expansion of human coloncancer- initiating cells. Nature. 2007;445:111-5. (Pubitemid 46067311)
95. Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007;104:10158-63.
96. Li X, Lewis MT, Huang J, Gutierrez C, Osborne CK, Wu MF, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100:672-9.
97. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106-30.
98. Boman BM, Huang E. Human colon cancer stem cells: a new paradigm in gastrointestinal oncology. J Clin Oncol. 2008;26:2828-38.
99. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432:396-401. (Pubitemid 39551674)
100. Trerotola M, Rathore S, Goel HL, Li J, Alberti S, Piantelli M, et al. CD133, Trop-2 and alpha2beta1 integrin surface receptors as markers of putative human prostate cancer stem cells. Am J Transl Res. 2010;2:135-44.
101. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646-74.
102. Shmelkov SV, Butler JM, Hooper AT, Hormigo A, Kushner J, Milde T, et al. CD133 expression is not restricted to stem cells, and both CD133? and CD133- metastatic colon cancer cells initiate tumors. J Clin Invest. 2008;118:2111-20. (Pubitemid 351872330)
103. Barker N, Ridgway RA, van Es JH, van de Wetering M, Begthel H, van den Born M, et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature. 2009;457:608-11.
104. Takahashi H, Ishii H, Nishida N, Takemasa I, Mizushima T, Ikeda M, et al. Significance of Lgr5(?ve) cancer stem cells in the colon and rectum. Ann Surg Oncol. 2011;18:1166-74.
105. Uchida H, Yamazaki K, Fukuma M, Yamada T, Hayashida T, Hasegawa H, et al. Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5 in colorectal cancer. Cancer Sci. 2010;101:1731-7.
106. Merlos-Suarez A, Barriga FM, Jung P, Iglesias M, Cespedes MV, Rossell D, et al. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse. Cell Stem Cell. 2011;8(5):511-24.
107. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74-108. (Pubitemid 40372904)
108. Clements WM, Wang J, Sarnaik A, Kim OJ, MacDonald J, Fenoglio-Preiser C, et al. beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res. 2002;62:3503-6. (Pubitemid 34651399)
109. Park WS, Oh RR, Park JY, Lee SH, Shin MS, Kim YS, et al. Frequent somatic mutations of the beta-catenin gene in intestinal- type gastric cancer. Cancer Res. 1999;59:4257-60. (Pubitemid 29418739)
110. Offerhaus GJ, Entius MM, Giardiello FM. Upper gastrointestinal polyps in familial adenomatous polyposis. Hepatogastroenterology. 1999;46:667-9. (Pubitemid 29224720)
111. Tomita H, Yamada Y, Oyama T, Hata K, Hirose Y, Hara A, et al. Development of gastric tumors in Apc(Min/?) mice by the activation of the beta-catenin/Tcf signaling pathway. Cancer Res. 2007;67:4079-87. (Pubitemid 46815052)