title: Mutations of p53, E-cadherin, alpha- and beta-catenin genes and tyrosine phosphorylation of beta-catenin in human gastric carcinomas.
abstract: We investigated whether dysfunction of p53 and E-cadherin participate in invasiveness and metastasis of human gastric carcinoma. We examined twenty-five human gastric carcinomas for p53, E-cadherin, alpha- and beta-catenin gene alteration by the reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) method and sequencing analysis. Three samples (13%) showed p53 gene mutation (two missense mutations and 6 bp deletion). 25% (3/12) of the carcinomas with lymph node metastasis had p53 gene mutations. One sample (4%) showed E-cadherin silent mutation. We were not able to detect alpha- or beta-catenin gene alteration. Therefore we investigated tyrosine-phosphorylation of E-cadherin, a and beta-catenin. Tyrosine-phosphorylated beta-catenin was detected in 13% (2/15) of poorly differentiated carcinomas. These results suggest that the p53 gene mutations have some correlation with lymph node metastasis, and tyrosine phosphorylation of beta-catenin rather than cadherin/catenin gene mutation is at least partly responsible for the loosening of cell-cell contact and invasiveness of poorly differentiated carcinomas.
authors.affiliation: NIHON UNIV,SCH MED,DEPT PHARMACOL,ITABASHI KU,TOKYO 173,JAPAN.
authors.forename: T
authors.initials: T
authors.lastname: Mazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Ishii
authors.forename: M
authors.initials: M
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Iwai
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa