title: Parallels between global transcriptional programs of polarizing Caco-2 intestinal epithelial cells in vitro and gene expression programs in normal colon and colon cancer.
abstract: Posttranslational mechanisms are implicated in the development of epithelial cell polarity, but little is known about the patterns of gene expression and transcriptional regulation during this process. We characterized temporal patterns of gene expression during cell-cell adhesion-initiated polarization of cultured human Caco-2 cells, which develop structural and functional polarity resembling enterocytes in vivo. A distinctive switch in gene expression patterns occurred upon formation of cell-cell contacts. Comparison to gene expression patterns in normal human colon and colon tumors revealed that the pattern in proliferating, nonpolarized Caco-2 cells paralleled patterns seen in human colon cancer in vivo, including expression of genes involved in cell proliferation. The pattern switched in polarized Caco-2 cells to one more closely resembling that in normal colon tissue, indicating that regulation of transcription underlying Caco-2 cell polarization is similar to that during enterocyte differentiation in vivo. Surprisingly, the temporal program of gene expression in polarizing Caco-2 cells involved changes in signaling pathways (e.g., Wnt, Hh, BMP, FGF) in patterns similar to those during migration and differentiation of intestinal epithelial cells in vivo, despite the absence of morphogen gradients and interactions with stromal cells characteristic of enterocyte differentiation in situ. The full data set is available at http://microarray-pubs.stanford.edu/CACO2.
authors: Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
authors: Annika M
authors: AM
authors: Sääf
authors: Jennifer M
authors: JM
authors: Halbleib
authors: Xin
authors: X
authors: Chen
authors: Siu Tsan
authors: ST
authors: Yuen
authors: Suet Yi
authors: SY
authors: Leung
authors: W James
authors: WJ
authors: Nelson
authors: Patrick O
authors: PO
authors: Brown
mesh_terms: D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation; D016764:Cell Polarity / Q000235:genetics*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051157:Frizzled Receptors / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006262:Health; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D051157:Frizzled Receptors; D020033:Protein Isoforms; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin
references: Nat Genet. 2004 Mar;36(3):277-82
references: 14770182
references: Science. 2004 Mar 5;303(5663):1483-7
references: 15001769
references: PLoS Biol. 2003 Oct;1(1):E5
references: 12929205
references: J Biol Chem. 2004 Apr 23;279(17):17232-40
references: 14960582
references: J Cell Biol. 2004 Jul 5;166(1):37-47
references: 15240568
references: Mol Cell Biol. 2004 Oct;24(20):8813-22
references: 15456857
references: Annu Rev Cell Dev Biol. 2004;20:695-723
references: 15473857
references: In Vitro. 1970 Sep-Oct;6(2):128-42
references: 4943054
references: Cell. 1991 Aug 9;66(3):589-600
references: 1651174
references: Nature. 1992 Sep 17;359(6392):235-7
references: 1528264
references: Cancer Res. 1992 Nov 1;52(21):5853-64
references: 1394214
references: J Cell Biol. 1994 Mar;124(5):729-41
references: 8120095
references: J Cell Biol. 1994 Jun;125(6):1327-40
references: 8207061
references: Cancer Res. 1995 Jul 1;55(13):2910-9
references: 7796420
references: Semin Nephrol. 1995 Jul;15(4):272-84
references: 7569407
references: Dev Biol. 1995 Nov;172(1):126-38
references: 7589793
references: Nature. 1996 Aug 15;382(6592):638-42
references: 8757136
references: Cell. 1996 Aug 9;86(3):391-9
references: 8756721
references: Cell Biol Int. 1996 Feb;20(2):139-46
references: 8935158
references: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5355-60
references: 9144241
references: EMBO J. 1997 Jul 1;16(13):3797-804
references: 9233789
references: Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10330-4
references: 9294210
references: Bioessays. 1997 Nov;19(11):949-57
references: 9394617
references: Genes Dev. 1997 Dec 15;11(24):3286-305
references: 9407023
references: EMBO J. 1998 Mar 2;17(5):1371-84
references: 9482734
references: Science. 1998 Apr 24;280(5363):596-9
references: 9554852
references: Curr Biol. 1998 May 7;8(10):573-81
references: 9601641
references: J Cell Sci. 1998 Jun;111 ( Pt 12):1741-9
references: 9601103
references: Nature. 1998 Oct 8;395(6702):604-8
references: 9783586
references: Nature. 1998 Oct 8;395(6702):608-12
references: 9783587
references: EMBO J. 2001 Jul 2;20(13):3427-36
references: 11432830
references: Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7795-800
references: 11416169
references: EMBO J. 2001 Aug 15;20(16):4500-11
references: 11500377
references: J Biol Chem. 2002 Jan 18;277(3):1884-91
references: 11711551
references: Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1182-7
references: 11818547
references: J Biol Chem. 2002 Feb 22;277(8):6428-37
references: 11704675
references: Nat Rev Cancer. 2001 Oct;1(1):55-67
references: 11900252
references: Mol Cell Biol. 2002 May;22(9):3129-39
references: 11940670
references: Eur J Cancer. 2002 May;38(7):867-71
references: 11978510
references: J Gastroenterol. 2002;37(4):239-46
references: 11993506
references: Cancer Res. 2002 Jun 1;62(11):3322-6
references: 12036951
references: Mol Biol Cell. 2002 Jun;13(6):1977-2000
references: 12058064
references: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8683-8
references: 12072559
references: Cancer Cell. 2002 Mar;1(2):145-55
references: 12086873
references: Mech Dev. 1998 Sep;77(1):75-80
references: 9784611
references: EMBO J. 1998 Dec 15;17(24):7351-60
references: 9857191
references: Am J Pathol. 1999 Jan;154(1):29-35
references: 9916915
references: Physiol Rev. 1999 Jan;79(1):73-98
references: 9922368
references: Am J Pathol. 1999 Feb;154(2):515-23
references: 10027409
references: EMBO J. 1999 May 4;18(9):2401-10
references: 10228155
references: J Cell Biol. 1999 May 17;145(4):741-56
references: 10330403
references: Cell. 1999 Jun 11;97(6):717-26
references: 10380924
references: Nature. 1999 Jun 24;399(6738):793-7
references: 10391246
references: Nature. 1999 Jun 24;399(6738):798-802
references: 10391247
references: Curr Biol. 1999 Jul 1;9(13):695-8
references: 10395542
references: JPEN J Parenter Enteral Nutr. 1999 Sep-Oct;23(5 Suppl):S83-8
references: 10483903
references: Science. 1999 Sep 17;285(5435):1923-6
references: 10489374
references: Development. 2005 Jan;132(2):279-89
references: 15590741
references: Nat Rev Mol Cell Biol. 2005 Mar;6(3):233-47
references: 15738988
references: Cytokine Growth Factor Rev. 2005 Apr;16(2):233-47
references: 15863038
references: Exp Cell Res. 2005 Jun 10;306(2):357-63
references: 15925592
references: Nature. 2005 Jun 16;435(7044):959-63
references: 15959515
references: Nature. 2005 Jun 16;435(7044):964-8
references: 15959516
references: Gastroenterology. 2005 Aug;129(2):626-38
references: 16083717
references: Int J Mol Med. 2006 Jan;17(1):171-5
references: 16328026
references: Ann N Y Acad Sci. 2005 Nov;1059:41-55
references: 16382042
references: Trends Cell Biol. 2006 Jan;16(1):45-54
references: 16337795
references: PLoS Biol. 2006 Apr;4(4):e115
references: 16602827
references: Nat Rev Genet. 2006 May;7(5):349-59
references: 16619050
references: FEBS Lett. 2006 May 22;580(12):2811-20
references: 16678165
references: Annu Rev Cell Dev Biol. 2006;22:287-309
references: 16824016
references: Cell. 2006 Nov 3;127(3):469-80
references: 17081971
references: Int J Mol Med. 2006 Dec;18(6):1019-23
references: 17089004
references: Curr Opin Cell Biol. 2006 Dec;18(6):616-22
references: 16962308
references: J Cell Biol. 2007 Feb 26;176(5):695-707
references: 17325209
references: Mol Biol Cell. 2007 Nov;18(11):4261-78
references: 17699590
references: J Biol Chem. 1985 Jan 10;260(1):139-46
references: 3965444
references: Am J Physiol. 1985 May;248(5 Pt 1):C410-8
references: 2986462
references: Cell. 1990 Feb 9;60(3):429-37
references: 2302734
references: Proc Natl Acad Sci U S A. 1990 Mar;87(5):1663-7
references: 1689846
references: Cell. 1990 Jun 1;61(5):759-67
references: 2188735
references: J Cell Biol. 1990 Oct;111(4):1351-61
references: 1976637
references: Oncogene. 2000 Jan 27;19(4):537-45
references: 10698523
references: J Biol Chem. 2000 Apr 28;275(17):12701-11
references: 10777564
references: EMBO J. 2000 May 2;19(9):2024-33
references: 10790369
references: Genes Dev. 2000 Jul 15;14(14):1741-9
references: 10898789
references: Genes Dev. 2000 Aug 1;14(15):1837-51
references: 10921899
references: Nature. 2000 Aug 17;406(6797):747-52
references: 10963602
references: Mol Biol Cell. 2000 Oct;11(10):3299-313
references: 11029037
references: Nucleic Acids Res. 2001 Apr 1;29(7):1410-9
references: 11266540
references: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references: 11309499
references: Biochim Biophys Acta. 2001 Apr 23;1538(2-3):260-72
references: 11336797
references: Nature. 2001 May 17;411(6835):349-54
references: 11357142
references: Biochem Biophys Res Commun. 2001 Apr 6;282(3):750-6
references: 11401527
references: Nat Genet. 2002 Oct;32(2):326-30
references: 12172548
references: Cell. 2002 Oct 18;111(2):241-50
references: 12408868
references: Cell. 2002 Oct 18;111(2):251-63
references: 12408869
references: Mol Cell Biol. 2003 Jan;23(1):131-9
references: 12482967
references: Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):337-48
references: 12787570
references: Nat Med. 2003 Jul;9(7):964-8
references: 12808448
references: Genes Dev. 2003 Jul 15;17(14):1709-13
references: 12865297
references: Dig Dis Sci. 2003 Aug;48(8):1523-9
references: 12924647
references: J Cell Biol. 2003 Sep 1;162(5):899-908
references: 12952940
references: Dev Cell. 2003 Sep;5(3):367-77
references: 12967557
references: Cancer Res. 2003 Dec 1;63(23):8323-9
references: 14678992
references: Gastroenterology. 2004 Jan;126(1):111-21
references: 14699493
references: J Cell Sci. 2004 Feb 1;117(Pt 4):559-70
references: 14709721
references: Oncogene. 2004 Feb 19;23(7):1377-91
references: 14973550