Colorectal cancer (CRC) is one of the major malignancies in the United States, accounting for 130,000 new cases and more than 50,000 deaths each year. Notably, the incidence and mortality rates from CRC have remained fairly constant over the past three decades despite advances in early detection and therapy. To develop effective prevention and therapeutic modalities for CRC an emergent challenge for cancer investigators is to identify and characterize the constellation of genetic factors that underlie CRC susceptibility. Key research tools are genetically defined mouse models such as the ApcMin/+ mouse. We have previously used the sensitized Min mouse to map and functionally clone a major modifier of Min-induced tumorigenesis, the secretory phospholipase Pla2g2a. This proposal extends our previous work by using the Min mouse to examine the phenotype of a conditional knockout of the nuclear receptor PPARg. Intercrosses between mice carrying floxxed alleles of PPARg, mice expressing the Cre recombinase driven by the intestine-specific villin promoter, and Min mice will provide Min test mice completely deficient for PPARg in the intestine. This experiment will unequivocally address the role of PPARg in Apc-mediated mouse colon tumorigenesis. Introduction of a wildtype Pla2g2a transgene into this test cross will examine potential genetic interactions between Pla2g2a and PPARg.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA105302-01
Application #
6728603
Study Section
Special Emphasis Panel (ZCA1-SRRB-Q (O1))
Program Officer
Macleod, Carol L
Project Start
2004-08-15
Project End
2006-07-31
Budget Start
2004-08-15
Budget End
2005-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$73,738
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biochemistry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
McAlpine, Christen A; Barak, Yaacov; Matise, Ilze et al. (2006) Intestinal-specific PPARgamma deficiency enhances tumorigenesis in ApcMin/+ mice. Int J Cancer 119:2339-46