Abstract

The Min mouse strain develops multiple intestinal neoplasms on sensitive genetic background. It is heterozygous for a nonsense allele of the Adenomatous polyposis coli gene of the mouse, Apc. We first shall aim to settle controversial issues concerning the strict adherence of adenoma formation to the one-locus Knudson model and the clonality of early tumors. Then, we shall explore the involvement of several candidate molecular systems in the Min phenotype, including the Wingless signaling pathway. Our work culminates in developing a sensitized genetic screen for mutant modifiers of the Min phenotypes. This screen, novel in mammalian cancer genetics, may identify a series of factors acting in this tumor lineage and in the tumor-bearing host.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37CA063677-05
Application #
2729415
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Marks, Cheryl L
Project Start
1993-09-22
Project End
2002-12-31
Budget Start
1998-03-01
Budget End
1998-12-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Pleiman, Jennifer K; Irving, Amy A; Wang, Zhishi et al. (2018) The conserved protective cyclic AMP-phosphodiesterase function PDE4B is expressed in the adenoma and adjacent normal colonic epithelium of mammals and silenced in colorectal cancer. PLoS Genet 14:e1007611
Pickhardt, Perry J (2015) Recent developments in colorectal imaging. Curr Opin Gastroenterol 31:76-80
Dove, William F; Shedlovsky, Alexandra; Clipson, Linda et al. (2014) A strategy to identify dominant point mutant modifiers of a quantitative trait. G3 (Bethesda) 4:1113-21
Pickhardt, Perry J; Kim, David H; Pooler, B Dustin et al. (2013) Assessment of volumetric growth rates of small colorectal polyps with CT colonography: a longitudinal study of natural history. Lancet Oncol 14:711-20
Thliveris, Andrew T; Clipson, Linda; Sommer, Lacy L et al. (2012) Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of Apc(Min) (/+) ROSA11 Gene Trap Mice. G3 (Bethesda) 2:569-78
Thliveris, Andrew T; Clipson, Linda; White, Alanna et al. (2011) Clonal structure of carcinogen-induced intestinal tumors in mice. Cancer Prev Res (Phila) 4:916-23
Durkee, Benjamin Y; Weichert, Jamey P; Halberg, Richard B (2010) Small animal micro-CT colonography. Methods 50:36-41
Halberg, Richard B; Waggoner, Jesse; Rasmussen, Kristen et al. (2009) Long-lived Min mice develop advanced intestinal cancers through a genetically conservative pathway. Cancer Res 69:5768-75
Huttlin, Edward L; Chen, Xiaodi; Barrett-Wilt, Gregory A et al. (2009) Discovery and validation of colonic tumor-associated proteins via metabolic labeling and stable isotopic dilution. Proc Natl Acad Sci U S A 106:17235-40
Durkee, Benjamin Y; Shinki, Kazuhiko; Newton, Michael A et al. (2009) Longitudinal assessment of colonic tumor fate in mice by computed tomography and optical colonoscopy. Acad Radiol 16:1475-82

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