Adult granulosa cell tumors (AGCTs) constitute a rare type of ovarian cancer that typically involves a specific mutation in the FOXL2 gene, which disrupts ovarian function and can lead to incurable relapse. However, it is not well understood how this specific mutation is able to promote cancer cell growth. To provide further mechanistic insights, researchers led by Tyler Hillman, M.D., Ph.D., examined cell lines of relapsed AGCT with this specific mutation.
They found that the mutation causes the FOXL2 protein to interact abnormally with the glucocorticoid receptor, which normally helps control gene expression for various cell processes. By changing how the glucocorticoid receptor binds to DNA, mutant FOXL2 promotes genes involved in cancer cell growth. The study uncovers the co-regulation between the FOXL2 mutation and glucocorticoid receptors, highlighting potential therapeutic targets for this patient population.