The E2A and inhibitor of
DNA binding (ID)
proteins are
transcription factors involved in cell cycle regulation and cellular differentiation. Imbalance of ID/E2A activity is associated with
oncogenesis in various
tumors, but their expression patterns and prognostic values are still unknown. We evaluated ID and E2A expression in
ovarian cancer cells, and assessed the possibility of reprogramming ovarian cellular homeostasis by restoring the ID/E2A axis. We analyzed copy number alterations, mutations, methylations, and
mRNA expressions of ID 1-4 and E2A using The
Cancer Genome Atlas data of 570 ovarian
serous cystadenocarcinoma patients. Incidentally, 97.2% cases exhibited gain of ID 1-4 or loss of E2A. Predominantly, ID 1-4 were hypomethylated, while E2A was hypermethylated. Immunohistochemical analysis revealed that ID-3 and ID-4 expressions were high while E2A expression was low in cancerous ovarian tissues. Correlation analysis of ID and E2A levels with survival outcomes of
ovarian cancer patients indicated that patients with high ID-3 levels had poor overall survival. We also determined the effect of E2A induction on
ovarian cancer cell growth in vitro and in vivo using SKOV-3/Luc cells transduced with
tamoxifen-inducible E47, a splice variant of E2A. Interestingly, E47 induced SKOV-3 cell death in vitro and inhibited
tumor growth in SKOV-3 implanted mice. Therefore, restoring ID/E2A balance is a promising approach for treating
ovarian cancer.