Overexpression of IL-4 Signaling Pathway to Inhibit Breast Tumor Growth
Abstract
The purpose of this research project was to characterize growth inhibitory effects of interleukin-4 (IL-4) in breast cancer cells and identify key signaling molecules which may be targets for future strategies to enhance the negative growth effects of WA. We have reported that IL-4-mediated growth inhibition is associated with increased apoptosis. Furthermore, we have identified that LA activates two important signaling molecules IRS-1 and STAT6. Inhibition of IRS-1 does not block IL-4-mediated growth effects while inhibition of STAT6 decreases IL-4-mediated growth inhibition and apoptosis. Additionally, over-expression of STAT6 mimics the effect of LA by decreasing growth and increasing apoptosis. In addition to these findings, we have also explored several other aspects of growth inhibition and apoptosis in breast cancer cells. We found that IGF-I is an effective mediator of survival following treatment with chemotherapy agents which induce apoptosis. Also, we have shown that the appearance of DNA laddering represents an end-stage processing mechanism that is not an accurate indicator of apoptosis in all strains of MCF-7 cells. Finally, we examined the mechanism of IFN gamma-mediated growth inhibition of breast cancer cells in vitro. In addition to the JAK-STAT pathway, interferon gamma decreases breast cancer cell growth in p2l dependent and independent pathways. In conclusion, our research on the mechanism and signal transduction pathways of IL-4 in human breast cancer cells has resulted in numerous original and significant findings as well as expanded our knowledge of mechanisms of apoptosis and growth inhibition of human breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2000
- Accession Number
- ADA384372
Entities
People
- Jennifer Gooch
Organizations
- University of Texas Health Science Center at San Antonio