The chance of developing invasive breast cancer during a woman's lifetime is approximately 1 in 8 and more than 40,000 women die of metastatic disease each year. Inherent or acquired tumor drug resistance and dose-limiting toxicity limit many agents used in the treatment of invasive breast cancer. Therefore, an important goal is the development of novel non-toxic therapeutic agents that are active against this deadly disease. We have preliminary data showing that mitochondrial catalase (mCAT) reduces metastatic progression of primary breast cancer in mice, suggesting that targeting mitochondria with catalase could be a potential strategy to treat or prevent metastatic breast cancer in women.
The aims of this proposal are 1) to further characterize the ability of mCAT to suppress breast cancer metastasis in mice;and 2) develop an inducible system in mice for controlling the expression of mCAT in a time and cell dependent manner. The data generated in this proposal would confirm our preliminary observations and provide the rationale for developing and/or testing clinically relevant mitochondrial-specific drug delivery systems for treating metastatic breast cancer.

Public Health Relevance

The project is designed to determine the ability of mitochondrially targeted catalase to suppress metastatic breast cancer in mice.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA140916-01
Application #
7707170
Study Section
Tumor Progression and Metastasis Study Section (TPM)
Program Officer
Forry, Suzanne L
Project Start
2009-07-17
Project End
2011-06-30
Budget Start
2009-07-17
Budget End
2010-06-30
Support Year
1
Fiscal Year
2009
Total Cost
$171,600
Indirect Cost
Name
University of Washington
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Goh, Jorming; Ladiges, Warren (2015) Voluntary Wheel Running in Mice. Curr Protoc Mouse Biol 5:283-290
Pettan-Brewer, Christina; Goh, Jorming; Ladiges, Warren C (2014) An immunohistochemical approach for monitoring effects of exercise on tumor stromal cells in old mice. Pathobiol Aging Age Relat Dis 4:
Goh, Jorming; Ladiges, Warren C (2014) Exercise enhances wound healing and prevents cancer progression during aging by targeting macrophage polarity. Mech Ageing Dev 139:41-8
Goh, Jorming; Endicott, Emma; Ladiges, Warren C (2014) Pre-tumor exercise decreases breast cancer in old mice in a distance-dependent manner. Am J Cancer Res 4:378-84
Goh, Jorming; Tsai, Jesse; Bammler, Theo K et al. (2013) Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner. PLoS One 8:e80123
Goh, Jorming; Ladiges, Warren C (2013) A novel long term short interval physical activity regime improves body composition in mice. BMC Res Notes 6:66
Fatemie, Sy; Goh, Jorming; Pettan-Brewer, Christina et al. (2012) Breast tumors in PyMT transgenic mice expressing mitochondrial catalase have decreased labeling for macrophages and endothelial cells. Pathobiol Aging Age Relat Dis 2:
Goh, Jorming; Enns, Linda; Fatemie, Soroosh et al. (2011) Mitochondrial targeted catalase suppresses invasive breast cancer in mice. BMC Cancer 11:191