POINT MUTATION OF THE E-CADHERIN GENE IN INVASIVE LOBULAR CARCINOMA OF THE BREAST
POINT MUTATION OF THE E-CADHERIN GENE IN INVASIVE LOBULAR CARCINOMA OF THE BREAST
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DOI：
10.1111/j.1349-7006.1994.tb02902.x
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发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
HIROHASHI, S
中科院分区：
文献类型：
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作者：
KANAI, Y;ODA, T;HIROHASHI, S
在低分化癌中，E-cadherin的表达减少或不均一，常表现为细胞间浸润性弱和显著的侵袭性。在体外，在以松散粘附方式生长的人癌细胞系中，不仅观察到E-钙粘蛋白的表达降低，而且观察到其结构异常。为了阐明E-cadherin结构异常在体内肿瘤侵袭中的作用，我们检测了cadherin结构域中的序列异常（外显子5、6、7和8），包括E-钙粘蛋白特异性结合所必需的区域，使用聚合酶链反应-单链构象多态性方法和直接测序在乳腺浸润性小叶癌中，其中癌细胞彼此分离并以特别分散的模式侵入基质。在20例检查中，有2例（10%）在E-钙粘蛋白外显子7中检测到相同的序列异常，即密码子315的点突变（AAT至AGT），导致单个氨基酸取代（天冬酰胺至丝氨酸）。这种突变可能会取消E-钙粘蛋白介导的细胞-细胞粘附，并至少部分负责弱的细胞间粘附和分散的组织学模式的肿瘤。
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.