FGF1 induces resistance to chemotherapy in ovarian granulosa tumor cells through regulation of p53 mitochondrial localization
Abstract
Ovarian cancer remains associated with a high mortality rate and relapse is too frequently seen after chemotherapeutic treatment of granulosa cell tumors (GCTs) or epithelial ovarian cancers (EOCs). It is thus of major importance to progress in the knowledge of the molecular mechanisms underlying chemoresistance of ovarian tumors. Overexpression of Fibroblast Growth Factor 1 (FGF1) is observed in various cancers, correlates with poor survival and could be responsible for resistance to platinum-based chemotherapy of serous ovarian cancers. How FGF1 promotes escape to chemotherapy remains unknown. In previous studies, we showed that FGF1 inhibits p53 transcriptional activities, leading to increased cell survival of neuronal or fibroblast cell lines. In this study, we show that FGF1 favors survival of COV434 cells upon treatment with etoposide and cisplatin, two common chemotherapeutic molecules used for ovarian cancer. Etoposide and cisplatin induced mitochondrial depolarization, cytochrome c release and caspase activation in COV434 cells. Overexpression of FGF1 counteracts these events and thus allows increased survival of ovarian cells. In this study, FGF1 had little effect on p53 stability and transcriptional activities. Etopo...Continue Reading
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