PMID- 10463574
OWN - NLM
STAT- MEDLINE
DCOM- 19990916
LR  - 20220331
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 16
DP  - 1999 Aug 15
TI  - Mutational activation of the beta-catenin proto-oncogene is a common event in the
      development of Wilms' tumors.
PG  - 3880-2
AB  - Activation of beta-catenin-mediated transcription is the nuclear end point of
      organ-specific Wnt signaling. In the developing kidney, Wnt-4, a secreted
      glycoprotein, acts as an autoinducer of the mesenchymal to epithelial transition 
      that underlies normal nephron development. Dysregulation of this epithelial
      transformation process may lead to Wilms' tumors (WTs). In this study, we
      investigated the potential role of the beta-catenin proto-oncogene, a candidate
      downstream target molecule of Wnt-4 signaling, in the development of WTs. In 6 of
      40 tumors (15%), mutation analysis revealed heterozygous missense mutations or
      small deletions that result in the loss of important regulatory phosphorylation
      sites within the beta-catenin protein. These findings indicate that activating
      beta-catenin mutations may play a significant role in the development of WTs and 
      establish a direct link between Wilms' tumorigenesis and the Wnt signal
      transduction pathway governing normal kidney development.
FAU - Koesters, R
AU  - Koesters R
AD  - Department of Surgery, University of Heidelberg, Germany.
      R.Koesters@DKFZ-Heidelberg.de
FAU - Ridder, R
AU  - Ridder R
FAU - Kopp-Schneider, A
AU  - Kopp-Schneider A
FAU - Betts, D
AU  - Betts D
FAU - Adams, V
AU  - Adams V
FAU - Niggli, F
AU  - Niggli F
FAU - Briner, J
AU  - Briner J
FAU - von Knebel Doeberitz, M
AU  - von Knebel Doeberitz M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (WNT4 protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt4 Protein)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Cytoskeletal Proteins/*genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genes, Tumor Suppressor
MH  - Genes, Wilms Tumor
MH  - Humans
MH  - Kidney Neoplasms/*genetics/pathology
MH  - *Mutation
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/*genetics
MH  - Signal Transduction/genetics
MH  - *Trans-Activators
MH  - Wilms Tumor/*genetics/pathology
MH  - Wnt Proteins
MH  - Wnt4 Protein
MH  - beta Catenin
EDAT- 1999/08/27 00:00
MHDA- 1999/08/27 00:01
CRDT- 1999/08/27 00:00
PHST- 1999/08/27 00:00 [pubmed]
PHST- 1999/08/27 00:01 [medline]
PHST- 1999/08/27 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Aug 15;59(16):3880-2.