Regulation of Cell Fate by Breast Tumor Kinase (BRK)
Abstract
Breast cancer is a heterogeneous disease, wherein the disregulation of numerous signaling pathways can cooperate to facilitate aberrant cell growth. We endeavored to understand how Brk, a soluble PTK overexpressed in nearly two-thirds of breast tumors, affects the development and progression of breast cancer. We studied Brk effects on cell viability by expressing GFP-Brk fusion proteins in breast cancer cells, and analyzed Annexin-V staining, indicative of apoptotic cell death, by flow cytometry. We found that Brk expression could increase the percentage of apoptotic cell death. Furthermore, we found that Brk inhibits the important cell survival molecule Akt, preventing Akt phosphorylation of the FOXO family member FKHR. In a separate line of investigation, we found that prolonged treatment of T47D breast cancer cells results in a biphasic pattern of Erk activation; the latent, sustained MAPK activation by progestins requires EGFR and MMP signaling, suggesting a positive, autocrine feedback mechanism of regulation. Significantly, progestin stimulation of breast cancer cell proliferation is sensitive to inhibitors of MAPK and EGFR signaling. By studying fundamental aspects of signal transduction in breast cancer, we hope to gain a better understanding of the molecular mechanisms of disease, thus facilitating a more informed approach to drug design.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427190
Entities
People
- Emily Faivre
Organizations
- University of Minnesota