Genetic Analysis of Ets-2 in Tumor-Associated Macrophages During Breast Cancer Progression
Abstract
While it is known that the most common human tumors are derived from epithelial cells that have undergone multiple genetic alterations, it is also becoming clear that the alterations in the tumor micro-environment are necessary for tumor progression. One such stromal component is the macrophage. Recent studies have shown that deletion of CSF-1, an essential growth factor for growth and differentiation of macrophages, delays pulmonary metastasis in the PyMT breast cancer model in mice. Previous work from our lab has demonstrated that Ets-2 is a nuclear effector of the Ras-Raf-MAP kinase pathway. My hypothesis is that CSF-1 mediates its pro-tumorigenic effects in macrophages via activation of Ets-2. To test this hypothesis, my project aims to analyze the effects of Ets-2 deletion specifically in the tumor-associated macrophages (TAMs) in the breast tumor microenvironment. To achieve this, I am using a conditional Ets-2 "floxed" allele available in our lab. I am using a non-inducible Lys-Cre transgene to delete Ets-2 specifically in the macrophages. Preliminary results with this system indicate that the gross tumor volume in the experimental animals is similar to that of the controls. Interestingly, the area of the lung lesions is significantly less in the experimentals as compared to those of the controls. At present I am trying to determine whether it is the exit from the primary tumor site or growth in the lungs which is affected in the experimentals. Microarray and real-time PCR analysis of mammary TAMs indicate that antiangiogenic factors may be downregulated in the Ets-2 deleted TAMs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2007
- Accession Number
- ADA477608
Entities
People
- Tahera Zabuawala
Organizations
- Ohio State University