TY - JOUR
T1 - Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis
AU - Derksen, Patrick W B
AU - Liu, Xiaoling
AU - Saridin, Francis
AU - van der Gulden, Hanneke
AU - Zevenhoven, John
AU - Evers, Bastiaan
AU - van Beijnum, Judy R.
AU - Griffioen, Arjan W.
AU - Vink, Jacqueline
AU - Krimpenfort, Paul
AU - Peterse, Johannes L.
AU - Cardiff, Robert
AU - Berns, Anton
AU - Jonkers, Jos
PY - 2006/11/1
Y1 - 2006/11/1
N2 - 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.
AB - 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.
KW - CELLCYCLE
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UR - http://www.scopus.com/inward/citedby.url?scp=33750614651&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2006.09.013
DO - 10.1016/j.ccr.2006.09.013
M3 - Article
C2 - 17097565
AN - SCOPUS:33750614651
VL - 10
SP - 437
EP - 449
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 5
ER -