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.
Pubmed ID: 17097565 RIS Download
Mesh terms: Animals | Anoikis | Breast Neoplasms | Cadherins | Carcinoma, Lobular | Disease Models, Animal | Female | Gene Silencing | Humans | Mammary Glands, Human | Mice | Mice, Inbred BALB C | Neoplasm Metastasis | Neovascularization, Pathologic | Skin Neoplasms | Survival Rate | Tumor Cells, Cultured | Tumor Suppressor Protein p53
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