title: Loss of functional E-cadherin renders cells more resistant to the apoptotic agent taxol in vitro.
abstract: Experimental evidence supports a role for E-cadherin in suppressing invasion, metastasis, and proliferation. Germline mutations of the E-cadherin represent the genetic cause of hereditary diffuse gastric cancer (HDGC). In this type of tumor, isolated cancer cells permeate the basal membrane and paradoxically survive in the gastric wall in the absence of contact with neighbor epithelial cells or with the extracellular matrix. This suggests that upon E-cadherin deregulation, cells acquired resistance to apoptosis. To test this hypothesis, CHO cells stably expressing either wild-type E-cadherin or the HDGC-related germline mutations T340A and V832M were seeded either on a thin layer of collagen type I or on plastic and then subjected to the apoptotic agent taxol. We found that in vitro functional E-cadherin renders cells more sensitive to the effect of taxol. Our results also indicate that this effect is associated to decreased level of the anti-apoptotic bcl-2 protein.
authors.affiliation: Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200 Porto, Portugal.
authors.forename: Paulo
authors.initials: P
authors.lastname: Ferreira
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Oliveira
authors.forename: Eliana
authors.initials: E
authors.lastname: Beraldi
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Mateus
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Martin
authors.initials: M
authors.lastname: Gleave
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Suriano
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016466:CHO Cells / Q000187:drug effects; D015820:Cadherins / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D005434:Flow Cytometry; D005562:Formazans / Q000494:pharmacology; D009154:Mutation; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013778:Tetrazolium Salts / Q000494:pharmacology; D014162:Transfection
chemical_list: D015820:Cadherins; D005562:Formazans; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; C079782:MTT formazan; D017239:Paclitaxel