Abstract
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.
Original language | English |
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Pages (from-to) | 437-49 |
Number of pages | 13 |
Journal | Cancer cell |
Volume | 10 |
Issue number | 5 |
DOIs | |
Publication status | Published - Nov 2006 |
Keywords
- Animals
- Anoikis/physiology
- Breast Neoplasms/metabolism
- Cadherins/genetics
- Carcinoma, Lobular/metabolism
- Disease Models, Animal
- Female
- Gene Silencing
- Humans
- Mammary Glands, Human/anatomy & histology
- Mice
- Mice, Inbred BALB C
- Neoplasm Metastasis
- Neovascularization, Pathologic
- Skin Neoplasms/metabolism
- Survival Rate
- Tumor Cells, Cultured
- Tumor Suppressor Protein p53/genetics