Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells

Hoshi,Reina; Watanabe,Yosuke; Ishizuka,Yoshiaki; Hirano,Takayuki; Nagasaki-Maeoka,Eri; Yoshizawa,Shinsuke; Uekusa,Shota; Kawashima,Hiroyuki; Ohashi,Kensuke; Sugito,Kiminobu; Fukuda,Noboru; Nagase,Hiroki; Soma,Masayoshi; Ozaki,Toshinori; Koshinaga,Tsugumichi; Fujiwara,Kyoko

doi:10.3892/or.2017.5477

Depletion of TFAP2E attenuates adriamycin-mediated apoptosis in human neuroblastoma cells

Authors:
- Reina Hoshi
- Yosuke Watanabe
- Yoshiaki Ishizuka
- Takayuki Hirano
- Eri Nagasaki-Maeoka
- Shinsuke Yoshizawa
- Shota Uekusa
- Hiroyuki Kawashima
- Kensuke Ohashi
- Kiminobu Sugito
- Noboru Fukuda
- Hiroki Nagase
- Masayoshi Soma
- Toshinori Ozaki
- Tsugumichi Koshinaga
- Kyoko Fujiwara
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Affiliations: Department of Pediatric Surgery, Nihon University School of Medicine, Itabashi, Tokyo 173-0032, Japan, Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-0032, Japan, Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan, Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Itabashi, Tokyo 173-0032, Japan, Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan
Published online on: February 24, 2017 https://doi.org/10.3892/or.2017.5477
Pages: 2459-2464

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Abstract

Neuroblastoma is a childhood malignancy originating from the sympathetic nervous system and accounts for approximately 15% of all pediatric cancer-related deaths. To newly identify gene(s) implicated in the progression of neuroblastoma, we investigated aberrantly methylated genomic regions in mouse skin tumors. Previously, we reported that TFAP2E, a member of activator protein-2 transcription factor family, is highly methylated within its intron and its expression is strongly suppressed in mouse skin tumors compared with the normal skin. In the present study, we analyzed public data of neuroblastoma patients and found that lower expression levels of TFAP2E are significantly associated with a shorter survival. The data indicate that TFAP2E acts as a tumor suppressor of neuroblastoma. Consistent with this notion, TFAP2E-depleted neuroblastoma NB1 and NB9 cells displayed a substantial resistance to DNA damage arising from adriamycin (ADR), cisplatin (CDDP) and ionizing radiation (IR). Silencing of TFAP2E caused a reduced ADR-induced proteolytic cleavage of caspase-3 and PARP. Of note, compared with the untransfected control cells, ADR-mediated stimulation of CDK inhibitor p21WAF1 was markedly upregulated in TFAP2E‑knocked down cells. Therefore, our present findings strongly suggest that TFAP2E has a pivotal role in the regulation of DNA damage response in NB cells through the induction of p21WAF1.

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