The SDF1-CXCR4 Axis Functions through p38-MAPK Signaling to Drive Breast Cancer Progression and Metastasis
Abstract
The primary long-term objective of this research is to understand how chemokine signaling through MAPK influences progression of breast carcinoma cells to a hormone-independent, endocrine therapy resistant and metastatic phenotype. Our preliminary evidence demonstrates that overexpression of CXCR4 in breast carcinoma cells leads to a hormone independent phenotype in vivo. The ability of CXCR4 expression to lead to estrogen independent breast tumor growth in immunocompromised mice is correlated with CXCR4 mediated activation of downstream signaling events and enhancement of estrogen receptor mediated gene expression. We hypothesize that altered expression of CXCR4 and activation by its ligand SDF1 directly controls progression to hormone independence in breast carcinoma cells. We specifically hypothesize that the SDF1-CXCR4 axis functions through G-protein coupled signaling through the downstream MAPK pathway to regulate gene expression. Our research will provide strong evidence that combining SDF1/CXCR4 blockade with current endocrine therapy strategies will be synergistically effective in treatment for endocrine resistant and metastatic breast cancer. As a novel mechanism of hormone independence this could prove to be a unique approach to beast cancer treatment. New treatment options for patients are necessary for improved patient care.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2007
- Accession Number
- ADA501240
Entities
People
- Lyndsey Vanhoy
Organizations
- Tulane University of Louisiana