title: Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment.
abstract: Invasion and dissemination of well-differentiated carcinomas are often associated with loss of epithelial differentiation and gain of mesenchyme-like capabilities of the tumor cells at the invasive front. However, when comparing central areas of primary colorectal carcinomas and corresponding metastases, we again found the same differentiated epithelial growth patterns. These characteristic phenotypic changes were associated with distinct expression patterns of beta-catenin, the main oncogenic protein in colorectal carcinomas, and E-cadherin. Nuclear beta-catenin was found in dedifferentiated mesenchyme-like tumor cells at the invasive front, but strikingly, as in central areas of the primary tumors, was localized to the membrane and cytoplasm in polarized epithelial tumor cells in the metastases. This expression pattern was accompanied by changes in E-cadherin expression and proliferative activity. On the basis of these data, we postulate that an important driving force for progression of well-differentiated colorectal carcinomas is the specific environment, initiating two transient phenotypic transition processes by modulating intracellular beta-catenin distribution in tumor cells.
authors.affiliation: Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstrasse 8-10, 91054 Erlangen, Germany. thomas.brabletz@patho.imed.uni-erlangen.de
authors.forename: T
authors.initials: T
authors.lastname: Brabletz
authors.forename: A
authors.initials: A
authors.lastname: Jung
authors.forename: S
authors.initials: S
authors.lastname: Reu
authors.forename: M
authors.initials: M
authors.lastname: Porzner
authors.forename: F
authors.initials: F
authors.lastname: Hlubek
authors.forename: L A
authors.initials: LA
authors.lastname: Kunz-Schughart
authors.forename: R
authors.initials: R
authors.lastname: Knuechel
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D002454:Cell Differentiation; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D017491:Genes, APC; D006801:Humans; D009361:Neoplasm Invasiveness; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D051176:beta Catenin