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

作者：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

来源：Oncology Reports, 2017, 37(4): 2459-2464.

DOI：10.3892/or.2017.5477

• neuroblastoma
• TFAP2E
• DNA damaging signal
• apoptosis
• tumor suppressor

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 p21(WAF1) 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 p21(WAF1).

• 出版日期2017-4