Data from PUMA Suppresses Intestinal Tumorigenesis in Mice

<div>Abstract<p>Defective apoptosis contributes to tumorigenesis, although the critical molecular targets remain to be fully characterized. PUMA, a BH3-only protein essential for p53-dependent apoptosis, has been shown to suppress lymphomagenesis. In this study, we investigated the role of PUMA in intestinal tumorigenesis using two animal models. In the azoxymethane (AOM)/dextran sulfate sodium salt model, <i>PUMA</i> deficiency increased the multiplicity and size of colon tumors but reduced the frequency of <i>β-catenin</i> hotspot mutations. The absence of <i>PUMA</i> led to a significantly elevated incidence of precursor lesions induced by AOM. AOM was found to induce p53-dependent PUMA expression and PUMA-dependent apoptosis in the colonic crypts and stem cell compartment. Furthermore, <i>PUMA</i> deficiency significantly enhanced the formation of spontaneous macroadenomas and microadenomas in the distal small intestine and colon of <i>APC</i>^Min/+ mice. These results show an essential role of PUMA-mediated apoptosis in suppressing intestinal tumorigenesis in mice. [Cancer Res 2009;69(12):4999–5006]</p></div>