The Role of Akt and its Substrates in Resistance of Breast Cancer to Trastuzumab
Abstract
The ability of Trastuzumab, a drug for treatment of HER2 overexpressing breast cancer, to induce apoptosis in HER2 overexpressing breast cancer lines was investigated. Particular attention was paid to the role of Akt downregulation by Trastuzumab and the resulting upregulation of pro-apoptotic Akt substrates. Trastuzumab was found to induce very little apoptosis and a few Akt substrates investigated Bad and FKHR were not affected by Trastuzumab treatment. Additional studies investigated the affect of Trastuzumab on the upregulation of the GLUT1 glucose transporter in HER2 overexpressing breast cancer cells. Trastuzumab inhibited the Cobalt-dependent induction of GLUT1. This indicates Trastuzumab may have affects on hypoxic tumors because Cobalt stimulation mimics a cell's response to hypoxia which results in induction of GLUT1 which in turn accelerates aerobic or anaerobic glycolysis for tumor growth and survival.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469240
Entities
People
- Christian D. Young
Organizations
- University of Colorado Boulder