E-cadherin is a tumour invasion suppressor gene mutated in human lobular breast cancers
E-cadherin is a tumour invasion suppressor gene mutated in human lobular breast cancers
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DOI：
10.1002/j.1460-2075.1995.tb00301.x
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发表时间：
1995-12-15
期刊：
影响因子：
11.4
通讯作者：
vanRoy, F
中科院分区：
文献类型：
--
作者：
Berx, G;CletonJansen, AM;vanRoy, F
令人信服的实验证据存在一个强大的细胞间粘附分子E-钙粘蛋白的侵袭抑制作用。此外，已建议对E-钙粘蛋白的肿瘤抑制作用。在人类癌症中，E-钙粘蛋白表达的部分或完全丧失与恶性相关。为了研究这种改变表达的分子基础，我们开发了一种全面的PCR/SSCP突变筛查人类E-cadherin基因，对49例乳腺癌患者的E-cadherin基因中肿瘤特异性突变的发生进行了检查。在42例浸润性导管或髓样乳腺癌样本中没有发现相关的DNA变化。相反，7例浸润性小叶乳腺癌中有4例在E-钙粘蛋白的细胞外部分存在蛋白质截短突变（3例无义突变和1例移码突变）。四个小叶癌E-cadherin突变显示肿瘤特异性杂合性丢失的染色体区域16q22.1包含E-cadherin基因座。在遵守这一点，没有E-钙粘蛋白的表达是可检测的免疫组化在这四个肿瘤。这些发现为浸润性小叶乳腺癌中典型的散在肿瘤细胞生长提供了分子学解释。
Compelling experimental evidence exists for a potent invasion suppressor role of the cell-cell adhesion molecule E-cadherin. In addition, a tumour suppressor effect has been suggested for E-cadherin. In human cancers, partial or complete loss of E-cadherin expression correlates with malignancy. To investigate the molecular basis for this altered expression we developed a comprehensive PCR/SSCP mutation screen for the human E-cadherin gene, For 49 breast cancer patients the occurrence of tumour-specific mutations in the E-cadherin gene was examined. No relevant DNA changes were encountered in any of 42 infiltrative ductal or medullary breast carcinoma samples, In contrast, four out of seven infiltrative lobular breast carcinomas harboured protein truncation mutations (three nonsense and one frameshift) in the extracellular part of the E-cadherin protein. Each of the four lobular carcinomas with E-cadherin mutations showed tumour-specific loss of heterozygosity of chromosomal region 16q22.1 containing the E-cadherin locus. In compliance with this, no E-cadherin expression was detectable by immunohistochemistry in these four tumours. These findings offer a molecular explanation for the typical scattered tumour cell growth in infiltrative lobular breast cancer.