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.
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Acknowledgments
This work is supported by the European Union Seventh Framework Programme FP7/2007–2013 under grant agreement number 2785668 and Cancer Research UK.
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Huels, D.J., Cammareri, P., Ridgway, R.A., Medema, J.P., Sansom, O.J. (2013). Methods to Assess Myc Function in Intestinal Homeostasis, Regeneration, and Tumorigenesis. In: Soucek, L., Sodir, N. (eds) The Myc Gene. Methods in Molecular Biology, vol 1012. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-429-6_16
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DOI: https://doi.org/10.1007/978-1-62703-429-6_16
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