title: Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front.
abstract: Sixty to eighty percent of all colorectal cancers are characterized by mutations in the APC tumor suppressor gene. Recently, it was shown that these mutations lead to a nuclear overexpression of beta-Catenin by disruption of the wingless/WNT signal pathway. Since nuclear beta-Catenin functions as a transcriptional activator of hitherto unknown tumor genes, this form of beta-Catenin is now considered a major oncoprotein in colorectal cancer. Using immunohistochemistry, we investigated the distribution of overexpressed beta-Catenin within individual colorectal carcinomas. In the majority of the tumors, we found no homogeneous staining, but a strong nuclear expression of beta-Catenin predominantly localized at the invasion front with strongest nuclear staining of isolated, scattered tumor cells. In contrast, cells in the tumor center often showed no nuclear staining, but retained a membranous expression of beta-Catenin, comparable to normal colon epithelium. It is, therefore, likely that in addition to the overexpression of beta-Catenin caused by defects in the APC locus, regulatory events in the tumor itself lead to a different distribution of this oncoprotein. Possibly, surrounding tissue at the invasion front can give signals to the tumor cells, leading to a nuclear translocation of beta-Catenin, where it may play a direct role in tumor invasion processes.
authors.affiliation: Department of Pathology, University of Erlangen-Nürnberg, Germany. Thomas.Brabletz@Patho.Med.Uni-Erlangen.de
authors.forename: T
authors.initials: T
authors.lastname: Brabletz
authors.forename: A
authors.initials: A
authors.lastname: Jung
authors.forename: K
authors.initials: K
authors.lastname: Hermann
authors.forename: K
authors.initials: K
authors.lastname: Günther
authors.forename: W
authors.initials: W
authors.lastname: Hohenberger
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness / Q000473:pathology; D015513:Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015513:Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin