Derksen Patrick W B, Liu Xiaoling, Saridin Francis, van der Gulden Hanneke, Zevenhoven John, Evers Bastiaan, van Beijnum Judy R, Griffioen Arjan W, Vink Jacqueline, Krimpenfort Paul, Peterse Johannes L, Cardiff Robert D, Berns Anton, Jonkers Jos
Division of Molecular Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Cancer Cell. 2006 Nov;10(5):437-49. doi: 10.1016/j.ccr.2006.09.013.
Metastatic disease is the primary cause of death in breast cancer, the most common malignancy in Western women. Loss of E-cadherin is associated with tumor metastasis, as well as with invasive lobular carcinoma (ILC), which accounts for 10%-15% of all breast cancers. To study the role of E-cadherin in breast oncogenesis, we have introduced conditional E-cadherin mutations into a mouse tumor model based on epithelium-specific knockout of p53. Combined loss of E-cadherin and p53 resulted in accelerated development of invasive and metastatic mammary carcinomas, which show strong resemblance to human ILC. Moreover, loss of E-cadherin induced anoikis resistance and facilitated angiogenesis, thus promoting metastatic disease. Our results suggest that loss of E-cadherin contributes to both mammary tumor initiation and metastasis.
转移性疾病是乳腺癌（西方女性中最常见的恶性肿瘤）死亡的主要原因。E-钙黏蛋白的缺失与肿瘤转移以及浸润性小叶癌（ILC）相关，ILC占所有乳腺癌的10%-15%。为了研究E-钙黏蛋白在乳腺肿瘤发生中的作用，我们将条件性E-钙黏蛋白突变引入基于p53上皮特异性敲除的小鼠肿瘤模型中。E-钙黏蛋白和p53的联合缺失导致侵袭性和转移性乳腺癌加速发展，与人类ILC极为相似。此外，E-钙黏蛋白的缺失诱导了失巢凋亡抗性并促进了血管生成，从而推动了转移性疾病的发展。我们的结果表明，E-钙黏蛋白的缺失促成了乳腺肿瘤的起始和转移。
