PMID- 10027409
OWN - NLM
STAT- MEDLINE
DCOM- 19990304
LR  - 20231105
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 154
IP  - 2
DP  - 1999 Feb
TI  - Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT 
      pathway.
PG  - 515-23
AB  - Overexpression of cell surface glycoproteins of the CD44 family is an early event 
      in the colorectal adenoma-carcinoma sequence. This suggests a link with 
      disruption of APC tumor suppressor protein-mediated regulation of 
      beta-catenin/Tcf-4 signaling, which is crucial in initiating tumorigenesis. To 
      explore this hypothesis, we analyzed CD44 expression in the intestinal mucosa of 
      mice and humans with genetic defects in either APC or Tcf-4, leading to 
      constitutive activation or blockade of the beta-catenin/Tcf-4 pathway, 
      respectively. We show that CD44 expression in the non-neoplastic intestinal 
      mucosa of Apc mutant mice is confined to the crypt epithelium but that CD44 is 
      strongly overexpressed in adenomas as well as in invasive carcinomas. This 
      overexpression includes the standard part of the CD44 (CD44s) as well as variant 
      exons (CD44v). Interestingly, deregulated CD44 expression is already present in 
      aberrant crypt foci with dysplasia (ACFs), the earliest detectable lesions of 
      colorectal neoplasia. Like ACFs of Apc-mutant mice, ACFs of familial adenomatous 
      polyposis (FAP) patients also overexpress CD44. In sharp contrast, Tcf-4 mutant 
      mice show a complete absence of CD44 in the epithelium of the small intestine. 
      This loss of CD44 concurs with loss of stem cell characteristics, shared with 
      adenoma cells. Our results indicate that CD44 expression is part of a genetic 
      program controlled by the beta-catenin/Tcf-4 signaling pathway and suggest a role 
      for CD44 in the generation and turnover of epithelial cells.
FAU - Wielenga, V J
AU  - Wielenga VJ
AD  - Department of Pathology, Academic Medical Center, University of Amsterdam, The 
      Netherlands.
FAU - Smits, R
AU  - Smits R
FAU - Korinek, V
AU  - Korinek V
FAU - Smit, L
AU  - Smit L
FAU - Kielman, M
AU  - Kielman M
FAU - Fodde, R
AU  - Fodde R
FAU - Clevers, H
AU  - Clevers H
FAU - Pals, S T
AU  - Pals ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Tcf7l2 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (Wnt Proteins)
RN  - 0 (Zebrafish Proteins)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Adenoma/metabolism/pathology
MH  - Adenomatous Polyposis Coli/genetics/metabolism/pathology
MH  - Adult
MH  - Animals
MH  - Carcinoma/metabolism/pathology
MH  - Cytoskeletal Proteins/genetics/*metabolism
MH  - DNA Primers/chemistry
MH  - DNA, Neoplasm/analysis
MH  - Female
MH  - Fluorescent Antibody Technique, Indirect
MH  - Genes, APC/*genetics
MH  - Humans
MH  - Hyaluronan Receptors/analysis/*biosynthesis
MH  - Intestinal Mucosa/metabolism/pathology
MH  - Intestinal Neoplasms/metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Proto-Oncogene Proteins/*metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - TCF Transcription Factors
MH  - *Trans-Activators
MH  - Transcription Factor 7-Like 2 Protein
MH  - Transcription Factors/*genetics
MH  - Wnt Proteins
MH  - *Zebrafish Proteins
MH  - beta Catenin
PMC - PMC1850011
EDAT- 1999/02/23 00:00
MHDA- 1999/02/23 00:01
PMCR- 1999/08/01
CRDT- 1999/02/23 00:00
PHST- 1999/02/23 00:00 [pubmed]
PHST- 1999/02/23 00:01 [medline]
PHST- 1999/02/23 00:00 [entrez]
PHST- 1999/08/01 00:00 [pmc-release]
AID - S0002-9440(10)65297-2 [pii]
AID - 1592 [pii]
AID - 10.1016/S0002-9440(10)65297-2 [doi]
PST - ppublish
SO  - Am J Pathol. 1999 Feb;154(2):515-23. doi: 10.1016/S0002-9440(10)65297-2.