PMID- 12408868
OWN - NLM
STAT- MEDLINE
DCOM- 20021112
LR  - 20220409
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 111
IP  - 2
DP  - 2002 Oct 18
TI  - The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal 
      cancer cells.
PG  - 241-50
AB  - The transactivation of TCF target genes induced by Wnt pathway mutations 
      constitutes the primary transforming event in colorectal cancer (CRC). We show 
      that disruption of beta-catenin/TCF-4 activity in CRC cells induces a rapid G1 
      arrest and blocks a genetic program that is physiologically active in the 
      proliferative compartment of colon crypts. Coincidently, an intestinal 
      differentiation program is induced. The TCF-4 target gene c-MYC plays a central 
      role in this switch by direct repression of the p21(CIP1/WAF1) promoter. 
      Following disruption of beta-catenin/TCF-4 activity, the decreased expression of 
      c-MYC releases p21(CIP1/WAF1) transcription, which in turn mediates G1 arrest and 
      differentiation. Thus, the beta-catenin/TCF-4 complex constitutes the master 
      switch that controls proliferation versus differentiation in healthy and 
      malignant intestinal epithelial cells.
FAU - van de Wetering, Marc
AU  - van de Wetering M
AD  - Department of Immunology and Center for Biomedical Genetics, University Medical 
      Center, 3584 CX, Utrecht, The Netherlands.
FAU - Sancho, Elena
AU  - Sancho E
FAU - Verweij, Cornelis
AU  - Verweij C
FAU - de Lau, Wim
AU  - de Lau W
FAU - Oving, Irma
AU  - Oving I
FAU - Hurlstone, Adam
AU  - Hurlstone A
FAU - van der Horn, Karin
AU  - van der Horn K
FAU - Batlle, Eduard
AU  - Batlle E
FAU - Coudreuse, Damien
AU  - Coudreuse D
FAU - Haramis, Anna Pavlina
AU  - Haramis AP
FAU - Tjon-Pon-Fong, Menno
AU  - Tjon-Pon-Fong M
FAU - Moerer, Petra
AU  - Moerer P
FAU - van den Born, Maaike
AU  - van den Born M
FAU - Soete, Gwen
AU  - Soete G
FAU - Pals, Steven
AU  - Pals S
FAU - Eilers, Martin
AU  - Eilers M
FAU - Medema, Rene
AU  - Medema R
FAU - Clevers, Hans
AU  - Clevers H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (CDKN1A protein, human)
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Cell Cycle
MH  - Cell Differentiation
MH  - Cell Division
MH  - Cell Transformation, Neoplastic
MH  - Colorectal Neoplasms/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/metabolism
MH  - Cytoskeletal Proteins/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Humans
MH  - Intestinal Mucosa/metabolism
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - TCF Transcription Factors
MH  - Trans-Activators/*genetics
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/*genetics
MH  - Tumor Cells, Cultured
MH  - beta Catenin
EDAT- 2002/11/01 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/11/01 04:00
PHST- 2002/11/01 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/11/01 04:00 [entrez]
AID - S0092867402010140 [pii]
AID - 10.1016/s0092-8674(02)01014-0 [doi]
PST - ppublish
SO  - Cell. 2002 Oct 18;111(2):241-50. doi: 10.1016/s0092-8674(02)01014-0.