Mazaki T, Ishii Y, Fujii M, Iwai S, Ishikawa K
NIHON UNIV,SCH MED,DEPT PHARMACOL,ITABASHI KU,TOKYO 173,JAPAN.
Int J Oncol. 1996 Sep;9(3):579-83. doi: 10.3892/ijo.9.3.579.
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.
我们研究了p53和E-钙黏蛋白功能障碍是否参与人类胃癌的侵袭和转移。我们采用逆转录-聚合酶链反应-单链构象多态性（RT-PCR-SSCP）方法和测序分析，检测了25例人类胃癌组织中的p53、E-钙黏蛋白、α-连环蛋白和β-连环蛋白基因改变。3个样本（13%）显示p53基因突变（2个错义突变和6bp缺失）。有淋巴结转移的癌组织中25%（3/12）存在p53基因突变。1个样本（4%）显示E-钙黏蛋白沉默突变。我们未检测到α-或β-连环蛋白基因改变。因此，我们研究了E-钙黏蛋白、α-连环蛋白和β-连环蛋白的酪氨酸磷酸化情况。在13%（2/15）的低分化癌组织中检测到酪氨酸磷酸化的β-连环蛋白。这些结果表明，p53基因突变与淋巴结转移存在一定相关性，β-连环蛋白的酪氨酸磷酸化而非钙黏蛋白/连环蛋白基因突变至少部分导致了低分化癌组织中细胞间接触的松散和侵袭性。
