Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis

Citation
Tr. Devereux et al., Mutation of beta-catenin is an early event in chemically induced mouse hepatocellular carcinogenesis, ONCOGENE, 18(33), 1999, pp. 4726-4733
Citations number
31
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
09509232 → ACNP
Volume
18
Issue
33
Year of publication
1999
Pages
4726 - 4733
Database
ISI
SICI code
0950-9232(19990819)18:33<4726:MOBIAE>2.0.ZU;2-H
Abstract
beta-catenin activation, and subsequent upregulation of Wnt-signaling, is a n important event in the development of certain human and rodent cancers. R ecently, mutations in the beta-catenin gene in the region of the serine-thr eonine glycogen kinase (GSK)-3 beta phosphorylation target sites have been identified in hepatocellular neoplasms from humans and transgenic mice. In this study we: examined 152 hepatocellular neoplasms from B6C3F1 mice inclu ded in five chemical treatment groups and controls for mutations in the bet a-catenin gene. Twenty of 29 hepatocellular neoplasms from mice treated wit h methyleugenol had point mutations at codons 32, 33, 33 or 41. sites which are mutated in colon and other cancers. Likewise, nine of 24 methylene chl oride-induced hepatocellular neoplasms and 18 of 42 oxazepam-induced neopla sms exhibited similar mutations. In contrast,only three of 18 vinyl carbama te-induced liver tumors, one of 18 TCDD-induced liver tumors, and two of 22 spontaneous liver neoplasms had mutations in beta-catenin. Thus. there app ears to be a chemical specific involvement of beta-catenin activation in mo use hepatocellular carcinogenesis. Expression analyses using Western blot a nd immunohistochemisty indicate that beta-catenin protein accumulates along cell membranes following mutation. The finding of mutations in both adenom as and carcinomas from diverse chemical treatment groups and the immunostai ning of beta-catenin protein in an altered hepatocellular focus suggest tha t these alterations are early events in mouse hepatocellular carcinogenesis .