title: Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis.
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.
authors.affiliation: Division of Molecular Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
authors.forename: Patrick W B
authors.initials: PW
authors.lastname: Derksen
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Liu
authors.forename: Francis
authors.initials: F
authors.lastname: Saridin
authors.forename: Hanneke
authors.initials: H
authors.lastname: van der Gulden
authors.forename: John
authors.initials: J
authors.lastname: Zevenhoven
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Evers
authors.forename: Judy R
authors.initials: JR
authors.lastname: van Beijnum
authors.forename: Arjan W
authors.initials: AW
authors.lastname: Griffioen
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vink
authors.forename: Paul
authors.initials: P
authors.lastname: Krimpenfort
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Peterse
authors.forename: Robert D
authors.initials: RD
authors.lastname: Cardiff
authors.forename: Anton
authors.initials: A
authors.lastname: Berns
authors.forename: Jos
authors.initials: J
authors.lastname: Jonkers
mesh_terms: D000818:Animals; D023102:Anoikis / Q000502:physiology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D020868:Gene Silencing; D006801:Humans; D042361:Mammary Glands, Human / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D016159:Tumor Suppressor Protein p53