C-KIT AND Stem Cell Factor Expression in Breast Cancer
Abstract
Coexpression of the tyrosine kinase growth factor receptor, c-kit, and its ligand, stem cell factor (SCF) is seen frequently in breast cancer. The MCF7 cell line (which only expresses SCF) transfected with a c-kit expression vector, shows enhanced growth in serum/free medium supplemented with EGF or lGF1. However, for the high Kit expressing KIBI subclone, the growth patterns for EGF + SCF are different than those of lGFI + SCF. lGF1 + SCF results in an additive growth for cells while EGF + SCF growth roughly equals that of EGF alone. One hypothesis is that if Kit and lGF1 mediate growth using different signal transduction pathways, there could be an additive growth effect. In contrast, if Kit and EGF signaling use the same pathway, this could become saturated. Differences in patterns of tyrosine phosphorylation are seen in lGF1 versus SCF stimulation of KIBI cells. A 90-95kD protein is phosphorylated at 10-15 minutes of SCF stimulation and is not present following lGF1 stimulation. Preliminary evidence suggests that it is not Stat 5. Tyrosine phosphorylation in the 40-50 kD range is also prominent. Active MAP kinase is present in KIBI cells stimulated with SCF but not in the low level Kit expressing cells, consistent with results of our growth studies where only the subclone with the greatest amount of Kit receptor responded to exogenous SCF. For both KIBI cells and KVAl cells, EGF and lGF1 produce MAP kinase activation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA369586
Entities
People
- Susan Hines
Organizations
- Virginia Commonwealth University