POINT MUTATION OF THE E-CADHERIN GENE IN INVASIVE LOBULAR CARCINOMA OF THE BREAST

被引:117
作者
KANAI, Y [1 ]
ODA, T [1 ]
TSUDA, H [1 ]
OCHIAI, A [1 ]
HIROHASHI, S [1 ]
机构
[1] NATL CANC CTR,RES INST,DIV PATHOL,CHUO KU,TOKYO 104,JAPAN
来源
JAPANESE JOURNAL OF CANCER RESEARCH | 1994年 / 85卷 / 10期
关键词
E-CADHERIN; GENETIC ABNORMALITY; INVASIVE LOBULAR CARCINOMA OF BREAST;
D O I
10.1111/j.1349-7006.1994.tb02902.x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Reduced or heterogeneous expression of E-cadherin has been demonstrated immunohistochemically in poorly differentiated carcinoma, which frequently shows weak intercellular adhesiveness and marked invasiveness. In vitro, not only reduced expression but also structural abnormalities of E-cadherin have been observed in human carcinoma cell lines which grow in a loosely adhering manner. To clarify the participation of structural abnormalities of E-cadherin in cancer invasion in vivo sequence abnormalities were examined in the cadherin domain (exons 5, 6, 7 and 8) including the region essential for E-cadherin specific binding, using the polymerase chain reaction-single-strand conformation polymorphism method and direct sequencing in invasive lobular carcinoma of the breast, in which cancer cells become detached from each other and invade the stroma in a particularly scattered pattern. In 2 (10%) of the 20 cases examined, an identical sequence abnormality was detected in E-cadherin exon 7, i.e. a point mutation of codon 315 (AAT to AGT) which resulted in a single amino acid substitution (asparagine to serine). This mutation may abolish the E-cadherin-mediated cell-cell adhesion and be at least partly responsible for the weak intercellular adhesiveness and scattered histological pattern of the tumor.
引用
收藏
页码:1035 / 1039
页数:5
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