| First Author | Harada N | Year | 2004 |
| Journal | Cancer Res | Volume | 64 |
| Issue | 1 | Pages | 48-54 |
| PubMed ID | 14729607 | Mgi Jnum | J:87481 |
| Mgi Id | MGI:2687179 | Doi | 10.1158/0008-5472.can-03-2123 |
| Citation | Harada N, et al. (2004) Hepatocarcinogenesis in mice with beta-catenin and Ha-ras gene mutations. Cancer Res 64(1):48-54 |
| abstractText | We have established previously a mouse strain containing a mutant beta-catenin allele of which exon 3 was sandwiched by loxP sequences [Catnb(lox(ex3))]. In this mouse strain, a Wnt-activating beta-catenin mutation alone is insufficient for hepatocarcinogenesis, but additional mutations or epigenetic changes may be required. Here we report that hepatocellular carcinoma develops at the 100% incidence in mice with simultaneous mutations in the beta-catenin and H-ras genes that are introduced by adenovirus-mediated Cre expression. Although H-ras mutation alone rapidly causes large cell dysplasia in the hepatocytes, these cells show no autonomous growth within 1 week after infection of the Cre-adenovirus. However, simultaneous induction of an additional mutation in the beta-catenin gene causes a clonal expansion of such dysplastic cells, followed by nodular formation and development of hepatocellular carcinoma. These results indicate that beta-catenin mutations play a critical role in hepatocarcinogenesis in cooperation with another oncogene and that these mice provide a convenient model to investigate early steps of hepatocarcinogenesis. |
