Characterization of Physiological Roles and Prognositc Importance of IR/IGF IR Hybrid Receptors in Breast Cancer
Abstract
Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been shown to have a role in breast cancer, although the specific importance of hybrid IR/IGF1R (Hybrid-R)is unknown. I proposed to use an inducible dimerization system to study Hybrid-R, and then optimize an assay to detect Hybrid-R in breast tumor samples. I constructed chimeric IR and IGF1R plasmids with different dimerization domains and developed stable MCF10A clones expressing only chimeric IR or chimeric IGF1R allowing homodimerization. Homodimerizer AP20187 treatment induced activation of chimeric IGF1R and IR in a dose dependent manner and activated AKT and ERK. However, I encountered technical difficulties in establishing cells expressing both chimeric IR and chimeric IGF1R and was unable to induce specific Hybrid-R. To measure the IR/IGF1R hybrid receptor on paraffin embedded specimens, a proximity ligation assay (PKLA) was optimized using both anti-IR and anti- IGF1R antibodies. The presence of PLA signals was increased in cells had IR or IGF1R overexpression and decreased in cells with IGF1R knock down. The variability of signals was also observed in a tissue microarray with normal breast tissue and breast tumor. This study shows the presence of Hybrid-R in breast cancer cell lines and human tumors and suggests that more studies are needed to determine its function and importance in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2012
- Accession Number
- ADA563074
Entities
People
- Yu-fen Wang
Organizations
- Baylor College of Medicine