title: Viral oncogene expression in the stem/progenitor cell compartment of the mouse intestine induces adenomatous polyps.
abstract: Genetic and epigenetic events that alter gene expression and/or protein function or localization are thought to be the primary mechanism that drives tumorigenesis and governs the clinical behavior of cancers. Yet, a number of studies have shown that the effects of oncogene expression or tumor suppressor ablation are highly dependent on cell type. The molecular basis for this cell-type specificity and how it contributes to tumorigenesis are unknown. Here, expression of a truncated SV40 large T antigen in murine intestinal crypts promoted the formation of numerous adenomatous polyps in the colon and small intestine. In contrast, when the same T-antigen construct is expressed in villous enterocytes, the consequences are limited to hyperplasia and dysplasia. The T-antigen-induced polyps show high levels of the proto-oncogene c-Myc protein even though there is no transport of β-catenin to the nucleus. Targeting the expression of viral oncogenes to intestinal crypts or villi provides a murine model system for studying cell-type specific effects in tumorigenesis, and is particularly relevant to the study of APC/β-catenin-independent pathways contributing to the generation of intestinal polyps.
  
  
  CONCLUSIONS
  This mouse model system describes the formation of colon polyps in the absence of Wnt/β-catenin signaling.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh. Pittsburgh, Pennsylvania.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sáenz Robles
authors.affiliation: Department of Human Genetics and Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: Jean Leon
authors.initials: JL
authors.lastname: Chong
authors.affiliation: Department of Human Genetics and Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: Christopher
authors.initials: C
authors.lastname: Koivisto
authors.affiliation: Department of Human Genetics and Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: Anthony
authors.initials: A
authors.lastname: Trimboli
authors.affiliation: Department of Human Genetics and Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: Huayang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Human Genetics and Cancer Center, Ohio State University, Columbus, Ohio.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Leone
authors.affiliation: Department of Biological Sciences, University of Pittsburgh. Pittsburgh, Pennsylvania. pipas@pitt.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Pipas
mesh_terms: D018256:Adenomatous Polyps / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D017209:Apoptosis; D063646:Carcinogenesis / Q000473:pathology; D002451:Cell Compartmentation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000952:Antigens, Polyomavirus Transforming; C000715470:MAS1 protein, human; D009856:Oncogene Proteins, Viral; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53