Role of Imatinib in Progesterone‐Dependent Breast Cancer Angiogenesis

Abstract

When human breast cancer MCF7 cells were treated with progesterone, our group found high expression of genes involved in Platelet-derived Growth Factor (PDGF) signalling pathway. PDGF expression in tumour cells is associated with increased angiogenic levels and its role in vessel stabilization is well established. The aim is to investigate whether blocking PDGF might be an antitumourigenic way in hormone-dependent breast cancer. Imatinib is a drug which interacts with specific Tyrosine-Kinase receptors such as c-KIT and PDGFR. Cultures of MCF7 cells, incubated with Progesterone or Progesterone+Imatinib were evaluated for viability, by MTT assay, apoptosis, by TUNEL assay, and migration, by Injury and Double-Chamber assays. Imunoexpression for PDGFR-α was accomplished by Western-blotting. Experiences using the same conditions in Endothelial Cells and Smooth Muscle Cells were addressed in our laboratory to investigate the interplay between progesterone and the role of PDGF in angiogenesis. Results seem to indicate that Imatinib-treated cells have higher apoptosis levels, poorer viability and less migration ability when compared to non-treated cell cultures. The findings obtained in this study, focusing the role of Imatinib in tumour angiogenesis can drive us to new therapeutic strategies against hormone-dependent cancers, which maintain a high incidence in our population. (Supported by Novartis).