Methods to assess Myc function in intestinal homeostasis, regeneration, and tumorigenesis

Huels, D.J., Cammareri, P., Ridgway, R.A., Medema, J.P. and Sansom, O.J. (2013) Methods to assess Myc function in intestinal homeostasis, regeneration, and tumorigenesis. Methods in Molecular Biology, 1012, pp. 237-248. (doi: 10.1007/978-1-62703-429-6_16)

Abstract

Within the intestinal epithelium, c-Myc has been characterized as a target of β-catenin-TCF signalling (He et al., Science 281:1509–1512, 1998). Given the most commonly mutated tumor suppressor gene within colorectal cancer (CRC) is the APC (Adenomatous Polyposis Coli) gene, a negative regulator of β-catenin-TCF signalling (Korinek et al., Science 275:1784–1787, 1997), loss of APC leads to Myc deregulation in the vast majority of CRC. This probably explains the numerous studies investigating c-Myc function within the intestinal epithelium. These have shown that c-Myc inhibition or deletion in the adult intestine results in proliferative defects (Muncan et al., Mol Cell Biol 26:8418–8426, 2006; Soucek et al., Nature 455:679–683, 2008). Importantly, intestinal enterocytes are able to survive in the absence of c-Myc which has allowed us (and others) to test the role of c-Myc in intestinal regeneration and tumorigenesis. Remarkably c-Myc deletion suppresses all the phenotypes of the Apc tumor suppressor gene loss and stops intestinal regeneration (Ashton et al., Dev Cell 19:259–269, 2010; Sansom et al., Oncogene 29:2585–2590, 2007). This suggests a clear therapeutic rationale for targeting c-Myc in CRC. Moreover haploinsufficiency for c-Myc in this tissue also reduces intestinal tumorigenesis (Athineos and Sansom, Oncogene 29:2585–2590, 2010; Yekkala and Baudino, Mol Cancer Res 5:1296–1303, 2007), and overexpression of c-Myc affects tissue homeostasis (Finch et al., Mol Cell Biol 29:5306–5315, 2009; Murphy et al., Cancer Cell 14:447–457, 2008). In this chapter we will provide an overview of our current laboratory protocols to characterize c-Myc function in intestinal homeostasis, regeneration, and tumorigenesis in vivo and in vitro.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ridgway, Dr Rachel and Cammareri, Dr Patrizia and Huels, Mr David and Sansom, Professor Owen
• Authors: Huels, D.J., Cammareri, P., Ridgway, R.A., Medema, J.P., and Sansom, O.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Methods in Molecular Biology
• ISSN: 1064-3745
• ISSN (Online): 1940-6029