title: PUMA suppresses intestinal tumorigenesis in mice.
abstract: 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, PUMA deficiency increased the multiplicity and size of colon tumors but reduced the frequency of beta-catenin hotspot mutations. The absence of PUMA 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, PUMA deficiency significantly enhanced the formation of spontaneous macroadenomas and microadenomas in the distal small intestine and colon of APC(Min/+) mice. These results show an essential role of PUMA-mediated apoptosis in suppressing intestinal tumorigenesis in mice.
authors.affiliation: Department of Pathology, University of Pittsburgh and Cancer Institute, Pittsburgh, Pennsylvania, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.forename: Eleanor B
authors.initials: EB
authors.lastname: Carson-Walter
authors.forename: Shih Fan
authors.initials: SF
authors.lastname: Kuan
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D015153:Blotting, Western; D017491:Genes, APC; D017403:In Situ Hybridization; D007414:Intestinal Neoplasms / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D051176:beta Catenin