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Association Between and Mutations and Progesterone Resistance in Endometriotic Epithelial Cell Line

Abstract

Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as or . Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that or mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including mutant and mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that mutation and mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, mutations may be associated with progesterone resistance in the context of pain.

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