Faculty Collaboration Database

Viral oncogene expression in the stem/progenitor cell compartment of the mouse intestine induces adenomatous polyps. Mol Cancer Res 2014 Oct;12(10):1355-64

Date

07/06/2014

Pubmed ID

24994749

Pubmed Central ID

PMC4201981

DOI

10.1158/1541-7786.MCR-14-0166

Scopus ID

2-s2.0-84907994320 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

UNLABELLED: 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.

IMPLICATIONS: This mouse model system describes the formation of colon polyps in the absence of Wnt/β-catenin signaling.

Author List

Sáenz Robles MT, Chong JL, Koivisto C, Trimboli A, Liu H, Leone G, Pipas JM

Authors

Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of Wisconsin
Anthony J. Trimboli PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenomatous Polyps
Animals
Antigens, Polyomavirus Transforming
Apoptosis
Carcinogenesis
Cell Compartmentation
Intestinal Mucosa
Intestines
Mice, Transgenic
Models, Biological
Mutation
Oncogene Proteins, Viral
Proto-Oncogene Proteins c-myc
Retinoblastoma Protein
Stem Cells
Tumor Suppressor Protein p53