Abstract 2908: The clinical significance of Nrf2 overexpression in esophageal cancer

Abstract

Abstract Background: NF-E2-related factor 2 (Nrf2) is a key transcription regulator for antioxidant and detoxification enzyme and is overexpressed in various cancer cells. In this study, prognostic significance of Nrf2 expression in esophageal cancer was investigated. In addition, we examined the relationship between the expression of Nrf2 and cell proliferation using in vitro assay. Methods: We immunohistochemically evaluated the protein expression of Nrf2 in the surgically resected specimens in 83 esophageal cancer patients. And ten esophageal cancer cell lines were utilized in vitro assay. Results: We examined the protein expression of Nrf2 in 10 esophageal cancer cell lines. TE-11 cell had the highest expression of Nrf2, while KYSE30 had the lowest expression of Nrf2. Importantly, there was no correlation between the protein level and mRNA level of Nrf2 in these cell lines. The cell proliferation was inhibited in TE-11 cells, and not inhibited in KYSE30 cells by treatment with Nrf2-siRNA. Moreover, Flow Cytometry Assay revealed that knockdown of Nrf2 by siRNA arrested the cell cycle at G1 phase in TE-11 cells. In immunohistological study, Nrf2 was predominantly identified in the nucleus of esophageal cancer cells and the expression level of Nrf2 was higher in the tumor than normal esophageal epithelium (P<0.001). There was no relationship between Nrf2 protein expression and clinicopathological characteristics. The overall survival of the high-Nrf2 expression group was significantly poorer than that of low-Nrf2 expression group (P = 0.004). Conclusions: The expression of Nrf2 is up-regulated in esophageal cancer cell lines and resected tumor specimen. Our in vitro assay revealed that Nrf2 appeared to support cancer cell proliferation. Therefore, strategies to pharmacologically manipulate the level and / or activity of Nrf2 may have potential to reduce tumor growth and improve the prognosis of esophageal cancer patients. Citation Format: Yuki Kitano, Yoshifumi Baba, Kensuke Yamamura, Hironobu Shigaki, Kousuke Mima, Junji Kurashige, Masaaki Iwatsuki, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Hideo Baba. The clinical significance of Nrf2 overexpression in esophageal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2908.