Overview of the molecular biology of hepatocellular neoplasms and hepatoblastomas of the mouse liver.

The molecular pathogenesis of chemically induced hepatocellular neoplasms and hepatoblastomas in the B6C3FI mouse is unclear but may involve alterations in the fi-catenin/Wnt signaling pathway as was recently described for human liver neoplasms. The objectives of this research were to characterize the mutation frequency and spectrum of P-catenin mutations and the intracellular localization of I-catenin protein accumulation in chemically induced hepatoblastomas and hepatocellular neoplasms. In the majority of the hepatoblastomas examined by immunohistochemical methods, both nuclear and cytoplasmic localization of P-catenin protein were detected, whereas in hepatocellular adenomas and carcinomas and normal liver only membrane staining was observed.

Cancer susceptibility of mice with a homozygous deletion in the COOH-terminal domain of the Brca2 gene.

Inherited mutations of the human BRCA2 gene confer increased risks for developing breast, ovarian, and several other cancers. Unlike previously described Brca2 knockout mice that display predominantly embryonic lethal phenotypes, we developed mice with a homozygous germ-line deletion of Brca2 exon 27 that exhibit a moderate decrease in perinatal viability and are fertile. We deleted this Brca2 COOH-terminal domain because it interacts directly with the Rad51 protein, contains a nuclear localization signal, and is required to maintain genomic stability in response to various types of DNA damage.