title: A causal role for E-cadherin in the transition from adenoma to carcinoma.
abstract: Development of malignant tumours is in part characterized by the ability of a tumour cell to overcome cell-cell adhesion and to invade surrounding tissue. E-cadherin is the main adhesion molecule of epithelia, and it has been implicated in carcinogenesis because it is frequently lost in human epithelial cancers. Re-establishing the functional cadherin complex in tumour cell lines results in a reversion from an invasive to a benign epithelial phenotype. However, it remained unresolved whether the loss of E-cadherin-mediated cell adhesion was a cause or a consequence of tumour progression in vivo. Here we report that the loss of E-cadherin expression coincides with the transition from well differentiated adenoma to invasive carcinoma in a transgenic mouse model of pancreatic beta-cell carcinogenesis (Rip1Tag2). Intercrossing Rip1Tag2 mice with transgenic mice that maintain E-cadherin expression in beta-tumour cells results in arrest of tumour development at the adenoma stage, whereas expression of a dominant-negative form of E-cadherin induces early invasion and metastasis. The results demonstrate that loss of E-cadherin-mediated cell adhesion is one rate-limiting step in the progression from adenoma to carcinoma.
authors.affiliation: Research Institute of Molecular Pathology, Vienna, Austria.
authors.forename: A K
authors.initials: AK
authors.lastname: Perl
authors.forename: P
authors.initials: P
authors.lastname: Wilgenbus
authors.forename: U
authors.initials: U
authors.lastname: Dahl
authors.forename: H
authors.initials: H
authors.lastname: Semb
authors.forename: G
authors.initials: G
authors.lastname: Christofori
mesh_terms: D007516:Adenoma, Islet Cell / Q000473:pathology*; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000502:physiology*; D018273:Carcinoma, Islet Cell / Q000209:etiology* / Q000473:pathology / Q000556:secondary; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007124:Immunoenzyme Techniques; D007515:Islets of Langerhans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D015820:Cadherins