| pubmed-article:9820866 | pubmed:abstractText | 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. | lld:pubmed |
