Role of Platelet-Derived Growth Factor C and Its Splice Variant in Breast Cancer

摘要

The aim of this project is to elucidate the role of Platelet-Derived Growth Factor C (PDGFC) and its splice variant, t-PDGFC, in breast cancer. This study has resulted in novel findings: Results show PDGFC expression to be associated with more aggressive characteristics. Data in vitro and in vivo show that higher expression of the PDGFC isoforms in breast cancer cell lines is associated with higher proliferation, invasion, and metastatic potential. Furthermore, this study has shown PDGFC in the nuclear fraction of breast cancer cell lines, suggesting an uncharacterized novel function in the nucleus. Additionally, t-PDGFC was believed to be exclusively an intracellular protein. However, new results in this project show that t-PDGFC can be secreted from breast cancer cells presumably as a hetero-dimer with FL-PDGFC. Thus, both FL- PDGFC and t-PDGFC can be intracellular and extracellular proteins. This marks an important paradigm shift for PDGFC, once typically thought of as primarily an extracellular signaling molecule. Taken together, my study has potentially important implications in the functional significance of PDGFC in breast cancer and how to target aberrant PDGFC signaling. Future drug targeting may need to take into account the intracellular and extracellular roles of both PDGFC isoforms in order to combat cancer.