Determining the Mechanism of Six1-Induced TRAIL Resistance and Its Role in Breast Cancer Metastasis
Annual summary 30 Sep 2010-29 Sep 2011
COLORADO UNIV AURORA CO
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Breast cancer is the most common cancer in women and the second deadliest. The gene Six1 is aberrantly expressed in half of all breast cancer tumors and in as much as 90 of metastatic tumors and has been shown to lead to increased tumor formation, increased metastasis and shorter survival. In addition, Six1 expression has been shown to confer resistance to TRAIL-induced apoptosis. In this project, we are identifying factors that contribute to this resistance. The TRAIL signaling pathway is part of the body s natural tumor surveillance program and may have a great impact on cells ability to form tumors and metastasize. In addition, the TRAIL signaling pathway is currently being exploited in clinical trials where resistance is an obstacle in achieving a response. By identifying markers of resistance and underlying mechanisms, resistance may be predicted and circumvented. In this project we have, in addition to assaying traditional apoptosis markers, performed a genome-wide shRNA library screen that could reveal novel genes that mediate TRAIL resistance in breast cancer, with a special focus on genes downstream of six1. Validation of these genes is currently underway.
- Anatomy and Physiology
- Medicine and Medical Research