Author/Authors :
Derksen، نويسنده , , Patrick W.B. and Liu، نويسنده , , Xiaoling and Saridin، نويسنده , , Francis and van der Gulden، نويسنده , , Hanneke and Zevenhoven، نويسنده , , John and Evers، نويسنده , , Bastiaan and van Beijnum، نويسنده , , Judy R. and Griffioen، نويسنده , , Arjan W. and Vink، نويسنده , , Jacqueline and Krimpenfort، نويسنده , , Paul and Peterse، نويسنده , , Johannes L. and Cardiff، نويسنده , , Robert D. and Berns، نويسنده , , Anton and Jonkers، نويسنده , , Jos، نويسنده ,
Abstract :
Summary
atic 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.
