| First Author | Jochem AS | Year | 2014 |
| Journal | Comp Med | Volume | 64 |
| Issue | 5 | Pages | 351-9 |
| PubMed ID | 25402175 | Mgi Jnum | J:312176 |
| Mgi Id | MGI:6783064 | Citation | Jochem AS, et al. (2014) c-Myc and transforming growth factor alpha enhance the development of hepatic lesions due to mutant beta-catenin in transgenic mice. Comp Med 64(5):351-9 |
| abstractText | Alterations in the Wnt signaling pathway are associated with diverse cancers, including hepatocellular carcinoma (HCC). The development of HCC is thought to be a multistage process in which multiple genetic alterations are necessary. Few studies have assessed the effect of aberrant Wnt signaling activity in association with other molecular alterations in HCC. Here we sought to determine whether co-overexpression of c-Myc or TGFalpha, 2 signaling molecules known to contribute to HCC development, enhanced the development of hepatic lesions associated with a stabilized beta-catenin. The coexpression of mutant beta-catenin with either c-Myc or TGFalpha within hepatocytes increased the severity of hepatic lesions compared with that associated with any of the transgenes expressed individually. The coexpression of mutant beta-catenin with c-Myc or TGFalpha resulted in severe hepatomegaly necessitating the euthanasia of mice by an average of 156 and 128 d, respectively, after the cessation of doxycycline. The expression of mutant beta-catenin alone resulted in mild to moderate hepatomegaly that prompted the euthanasia of mice by an average of 75 d after the cessation of doxycycline. Collectively, these findings indicate that coexpression of c-Myc or TGFalpha delays the onset of endstage hepatic disease yet enhances the severity of hepatic lesions due to mutant beta-catenin. |
