PMID- 10213482
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20091119
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 8
DP  - 1999 Apr 15
TI  - Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid 
      carcinoma.
PG  - 1811-5
AB  - Beta-catenin is an ubiquitously expressed cytoplasmic protein that has a crucial 
      role in both E-cadherin-mediated cell-cell adhesion and as a downstream signaling
      molecule in the wingless pathway. Stabilization of beta-catenin followed by
      nuclear translocation and subsequent T-cell factor/lymphoid-enhancing
      factor-mediated transcriptional activation has been proposed as an important step
      in oncogenesis. Stabilization may occur through activating mutations in exon-3 at
      the phosphorylation sites for ubiquitination and degradation of beta-catenin.
      Immunohistochemical subcellular localization of beta-catenin and mutational
      analysis of exon-3 of the beta-catenin gene by single-strand conformational
      polymorphism followed by DNA sequencing was performed on 37 samples from 31
      patients with anaplastic thyroid carcinoma. Immunofluorescent staining showed
      nuclear localization in 15 (42%) of the 36 samples examined. Nucleotide
      sequencing of mobility shifts detected by single-strand conformational
      polymorphism revealed somatic alterations in 19 (61%) of the 31 patients
      analyzed. We conclude that mutations in beta-catenin are common in anaplastic
      thyroid cancer and that they may activate transcription, as illustrated by
      frequent nuclear localization of the protein. These findings support the idea
      that beta-catenin acts as an oncogene and contributes to the highly aggressive
      behavior of this tumor.
FAU - Garcia-Rostan, G
AU  - Garcia-Rostan G
AD  - Department of Pathology, Yale University School of Medicine, New Haven,
      Connecticut 06520, USA. ginesa.rostan@yale.edu
FAU - Tallini, G
AU  - Tallini G
FAU - Herrero, A
AU  - Herrero A
FAU - D'Aquila, T G
AU  - D'Aquila TG
FAU - Carcangiu, M L
AU  - Carcangiu ML
FAU - Rimm, D L
AU  - Rimm DL
LA  - eng
GR  - R0-1 GM57604/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Amino Acid Sequence
MH  - Calcium-Calmodulin-Dependent Protein Kinases/genetics/metabolism
MH  - Carcinoma/*genetics/metabolism/pathology
MH  - Cell Nucleus/metabolism
MH  - Cytoskeletal Proteins/*genetics/metabolism
MH  - Exons/genetics
MH  - Fluorescent Antibody Technique
MH  - Glycogen Synthase Kinase 3
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorylation
MH  - Thyroid Neoplasms/*genetics/metabolism/pathology
MH  - *Trans-Activators
MH  - beta Catenin
EDAT- 1999/04/23 00:00
MHDA- 1999/04/23 00:01
CRDT- 1999/04/23 00:00
PHST- 1999/04/23 00:00 [pubmed]
PHST- 1999/04/23 00:01 [medline]
PHST- 1999/04/23 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Apr 15;59(8):1811-5.