B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver

Reed, K. R., Athineos, D., Meniel, V. S., Wilkins, J. A., Ridgway, .A., Burke, Z. D., Muncan, V., Clarke, A. R. and Sansom, O.J. (2008) B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. Proceedings of the National Academy of Sciences of the United States of America, 105(48), pp. 18919-18923. (doi: 10.1073/pnas.0805778105)

Abstract

Dysregulated Writ signaling is seen in approximately 30% of hepatocellular carcinomas; thus, finding pathways downstream of the activation of Writ signaling is key. Here, using cre-lox technology, we deleted the Apc gene in the adult mouse liver and observed a rapid increase in nuclear beta-catenin and c-Myc, which is associated with an induction of proliferation that led to hepatomegaly within 4 days of gene deletion. To investigate the downstream pathways responsible for these phenotypes, we analyzed the impact of inactivating APC in the context of deficiency of the potentially key effectors beta-catenin and c-Myc. beta-catenin loss rescues both the proliferation and hepatomegaly phenotypes after APC loss. However, c-Myc deletion, which rescues the phenotypes of APC loss in the intestine, had no effect on the phenotypes of APC loss in the liver. The consequences of the deregulation of the Writ pathway within the liver are therefore strikingly different from those observed within the intestine, with the vast majority of Writ targets being beta-catenin-dependent but c-Myc-independent in the liver.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ridgway, Dr Rachel and Athineos, Mr Dimitris and Sansom, Professor Owen
• Authors: Reed, K. R., Athineos, D., Meniel, V. S., Wilkins, J. A., Ridgway, .A., Burke, Z. D., Muncan, V., Clarke, A. R., and Sansom, O.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490