Functional characterization of a novel transcript of ERCC1 in chemotherapy resistance of ovarian cancer

Abstract

Approximately 15-20% of ovarian cancer patients receiving platinum-based chemotherapy are primary platinum-resistant. Identification of these patients and transfer to other more effective therapy could reduce the morbidity of ovarian cancer. ERCC1 is a DNA repair gene which can complex with XPF to repair cisplatin-induced DNA damage and cause chemotherapy resistance. In this study, we found a novel ERCC1 transcript initiated upstream of the normal transcription initiation site. The expression of this larger ERCC1 transcript dramatically increased following cisplatin treatment in ovarian cancer cells and was regulated by the MAPK pathway. This phenomenon conferred enhanced cisplatin resistance on ovarian cancer cells, and was confirmed with chemosensitive and chemoresistant patients' samples. Our data suggested that larger ERCC1 transcript levels correlated with the outcome of platinum-based chemotherapy.