PMID- 10076565
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190513
IS  - 0910-5050 (Print)
IS  - 0910-5050 (Linking)
VI  - 90
IP  - 1
DP  - 1999 Jan
TI  - Mutations of the beta-catenin gene in endometrial carcinomas.
PG  - 55-9
AB  - To investigate the contribution of beta-catenin to the development of endometrial
      carcinoma, we searched for genetic alterations of the beta-catenin gene in
      primary endometrial carcinomas. Mutational analysis of exon 3 of the beta-catenin
      gene, encoding the serine/threonine residues for GSK-3 beta phosphorylation, was 
      performed for 35 tumors. Nucleotide sequencing analysis revealed that 5 tumors
      (5/35, 14%) contained mutations (S33C, S37C, S37F, T41A) that altered potential
      GSK-3 beta phosphorylation sites. Each of the mutations resulted in the
      substitution of serine/threonine residues that have been implicated in the
      down-regulation of beta-catenin through phosphorylation by GSK-3 beta kinase.
      Furthermore, the incidence of beta-catenin mutations was significantly higher in 
      early-onset (3 of 5) than that in late-onset tumors (2 of 30) (P = 0.014,
      Fisher's exact test). Replication error (RER)-positive phenotype was not detected
      in tumors with the beta-catenin gene mutation, although 10 of 35 tumors revealed 
      RER. We performed immunohistochemistry of beta-catenin in 17 cases for which
      tissue samples were available. We confirmed accumulation of beta-catenin protein 
      in both the nucleus and cytoplasm in 3 tumors, including two in which amino acid 
      alterations had occurred at codon 33 and 37. The other case had no mutation in
      exon 3. Our results suggested that mutations at serine/threonine residues
      involved in phosphorylation by GSK-3 beta affected the stability of beta-catenin.
      Accumulation of mutant beta-catenin could contribute to the development of a
      subset of endometrial carcinomas, particularly those of the early-onset type.
FAU - Kobayashi, K
AU  - Kobayashi K
AD  - Department of Obstetrics and Gynecology, Sapporo Medical University, School of
      Medicine, Hokkaido.
FAU - Sagae, S
AU  - Sagae S
FAU - Nishioka, Y
AU  - Nishioka Y
FAU - Tokino, T
AU  - Tokino T
FAU - Kudo, R
AU  - Kudo R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Jpn J Cancer Res
JT  - Japanese journal of cancer research : Gann
JID - 8509412
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (Cadherins)
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 Substitution
MH  - Cadherins/genetics
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cytoskeletal Proteins/*genetics/metabolism
MH  - Endometrial Neoplasms/*genetics
MH  - Exons
MH  - Female
MH  - Gene Rearrangement
MH  - Glycogen Synthase Kinase 3
MH  - Heterozygote
MH  - Humans
MH  - Phosphorylation
MH  - *Point Mutation
MH  - Polymorphism, Single-Stranded Conformational
MH  - Substrate Specificity
MH  - *Trans-Activators
MH  - beta Catenin
PMC - PMC5925974
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
AID - S0910505099800271 [pii]
AID - 10.1111/j.1349-7006.1999.tb00665.x [doi]
PST - ppublish
SO  - Jpn J Cancer Res. 1999 Jan;90(1):55-9. doi: 10.1111/j.1349-7006.1999.tb00665.x.