Targeting Nuclear FGF Receptor to Improve Chemotherapy Response in Triple-Negative Breast Cancer
Abstract
Our studies during this grant period identified a function for nuclear basic fibroblast growth factor (bFGF) in TN breast cancer chemo-resistance using a short-term chemotherapy treatment model of resistance. We also showed that nuclear bFGF expression was increased in tumor cells of TN breast cancer patients post-chemotherapy treatment, validating our invitro model. We determined that FGF receptor 1 (FGFR1) protein, but not FGF receptor 3 (FGFR3) protein, was upregulated in chemotherapy-resistant SUM159 tumor cells (compared to that in untreated SUM159 cells). SUM159 TN tumor cell lines expressing FGFR1 shRNAs or control shRNAs were produced. Using these lines, we showed that FGFR1 knockdown reducesSnail-1 protein levels, providing support for our hypothesis that an FGF receptor regulates Snail-1 transcription to drive chemotherapy resistance. We will use these shRNA transfectants in year 3 to investigate a function for an FGFR1/Snail-1signaling axis in TN breast cancer chemo-resistance. Having shown in year 1 that FGFR inhibitors block the growth of chemo-resistant TN breast tumor cells, we will investigate the hypothesis in year 3 that this activity is attributable to FGFR inhibitor suppression of FGFR1 activity. Finally, we will optimize an IHC protocol for detecting FGFR1 in tumor cells of TNBC patients pre- and post- neoadjuvant chemotherapy treatment. These studies will investigate FGFR1 as a marker of chemo-resistance in TN breast cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2015
- Accession Number
- AD1007139
Entities
People
- Robin E. Bachelder
Organizations
- Duke University