Abstract PR03: GLUT1 is required for induction of mammary tumorigenesis by activated ErbB2/HER2/Neu

Alterations in tumor cell metabolism have been investigated for decades, and include changes in glucose utilization, as well as changes in mitochondrial and fatty acid metabolism; however, it is unclear at what point during the process of tumorigenesis these metabolic changes occur. We hypothesized that elevated glucose uptake represents the first metabolic adaptation to transformation, and thus may be a target for the prevention of breast cancer. The GLUT1 transporter is expressed in breast cancer cells and is responsible for the majority of their glucose uptake. Not surprisingly, breast cancer patients with high levels of GLUT1 have a poorer clinical outcome than those with lower levels, likely due to the association between glucose uptake and high tumor grade. We previously showed that the reduction of GLUT1 in established tumor cells resulted in a 50% decrease in glucose consumption and lactate generation. There was a corresponding decrease in proliferation in both two and three-dimensional culture, and in tumor growth in immunodeficient mice. Mammary epithelial cells from GLUT1fl/fl mice were transformed using polyoma middle tumor antigen (PyMT), and GLUT1 excised using Cre recombinase. Cells expressing GLUT1 were tumorigenic in immunodeficient mice, while cells lacking GLUT1 were not tumorigenic. This suggests that in mammary epithelial cells transformed in vitro, loss of GLUT1 was sufficient to prevent tumor outgrowths when injected into the mammary fat pad of nude mic...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Animal Models: Oral Presentations - Proffered Abstracts Source Type: research