Contrary, in progestin-resistant endometrial cancer (EC) cells, SIRT1 knockout (SIRT1-KO) results in the upregulation of progesterone receptor (PR) and FOXO1, as well as the downregulation of sterol regulatory element-binding protein-1 (SREBP-1) that increases sensitivity to progestin therapy. The gene discussed is SIRT1; the disease is endometrial cancer.