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Article

Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47

1
Department of Obstetrics and Gynecology, Institute of Women’s Medical Life Science, Yonsei University College of Medicine, Seoul 03722, Korea
2
Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA
*
Authors to whom correspondence should be addressed.
Academic Editors: Marcin Iwanicki and Mikołaj Piotr Zaborowski
Cancers 2022, 14(12), 2903; https://doi.org/10.3390/cancers14122903
Received: 4 May 2022 / Revised: 5 June 2022 / Accepted: 8 June 2022 / Published: 12 June 2022
Ovarian cancer is one of the most fatal gynecological malignancies in women. Even though primary treatment might result in complete remission, approximately 60–80% patients with advanced-stage ovarian cancer experience a relapse. To improve their survival outcomes, several novel agents have been proposed; however, the majority of these have demonstrated limited efficacy in the treatment of ovarian cancer. Interestingly, an imbalance in the basic helix-loop-helix inhibitor of DNA binding (bHLH/ID) protein networks has been associated with oncogenesis, but the exact expression patterns of bHLH/ID in ovarian cancer are not yet known. We hypothesized that such an imbalance in bHLH/ID activity may be integral to ovarian cancer pathogenesis, and modulating the bHLH/ID balance might be a promising approach to treat ovarian cancer.
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. View Full-Text
Keywords: ovarian cancer; basic helix-loop-helix protein; inhibitor of DNA binding; transcription factor-3; bHLH/ID complex ovarian cancer; basic helix-loop-helix protein; inhibitor of DNA binding; transcription factor-3; bHLH/ID complex
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MDPI and ACS Style

Lee, Y.-J.; Nam, E.-J.; Kim, S.; Kim, Y.-T.; Itkin-Ansari, P.; Kim, S.-W. Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47. Cancers 2022, 14, 2903. https://doi.org/10.3390/cancers14122903

AMA Style

Lee Y-J, Nam E-J, Kim S, Kim Y-T, Itkin-Ansari P, Kim S-W. Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47. Cancers. 2022; 14(12):2903. https://doi.org/10.3390/cancers14122903

Chicago/Turabian Style

Lee, Yong-Jae, Eun-Ji Nam, Sunghoon Kim, Young-Tae Kim, Pamela Itkin-Ansari, and Sang-Wun Kim. 2022. "Expression Profiles of ID and E2A in Ovarian Cancer and Suppression of Ovarian Cancer by the E2A Isoform E47" Cancers 14, no. 12: 2903. https://doi.org/10.3390/cancers14122903

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