Hepatocyte nuclear factor 1ß (HNF1ß) is expressed only in ovarian clear cell carcinoma (OCCC) and is characteristic of OCCC. This phenomenon is a unique feature of OCCC, including resistance to chemotherapy. However, the biological role of HNF1ß in OCCC is not clearly understood yet. Comprehensive metabolomic analysis using the stable cell lines transfected with HNF1ß-shRNA showed that HNF1ß dramatically changes intracellular metabolism, in particular, induction of aerobic glycolysis, the so-called “Warburg effect”. Only when the supply of glucose is enough, HNF1ß causes metabolic changes and is thus involved in cell survival under stress such as hypoxia and chemical reagents. Enhanced cell survival is based on a reduction in ROS activity resulting from metabolic changes such as the transition from oxidative phosphorylation to glycolysis and an increase in the intracellular antioxidant glutathione (GSH). One of the cystine transporters, rBAT, may be involved in increasing GSH. These data indicate that HNF1ß induced in the endometriotic cyst microenvironment confers a survival advantage on epithelial cells. In other words, the expression of HNF1ß is considered to be the cause of OCCC chemotherapy resistance.
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