Overexpression of IL-4 Signaling Pathway to Inhibit Breast Tumor Growth
Abstract
The purpose of this research was to characterize growth inhibition by 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 IL-4. We had previously characterized IL-4 receptor expression in human breast cancer cell lines and identified IL-4-mediated apoptosis. We considered that IL-4 may be signaling through two pathways : the IRS-1 pathway which could potentially be share with the insulin-like growth factor (IGF) mitogenic pathway, and the STAT6 transcrition pathway. After inhibiting IRS-I protein with inducible anti- sense IRS-1 fragment expression, we concluded that IRS-1 isr equired for IGF-1-mediated growth effects, but not IL-4-mediated growth effects. Therefore, we examined the role of STAT6 and found that inhibition of STAT6 through expression of a dominant-negative STAT6 protein resulted in a loss of IL-4-mediated growth inhibiting and apoptosis. Therefore, we have found that IL-4-mediated growth inhibition and induction of apoptosis in human breast cancer cells requires STAT6 and not IRS-1. Therefore, we can direct fliture experiments to flirther characterization and manipulation of STAT6 to enhance IL-4-mediated growth effects.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA385504
Entities
People
- Jennifer L. Gooch
Organizations
- University of Texas at Austin