Yoon Tae Mi, Kim Sun-Ae, Lee Dong Hoon, Lee Joon Kyoo, Park Young-Lan, Lee Kyung-Hwa, Chung Ik-Joo, Joo Young-Eun, Lim Sang Chul
Department of Otorhinolaryngology-Head and Neck Surgery, Chonnam National University Medical School, Gwangju, Republic of Korea.
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
Oncol Rep. 2015 Apr;33(4):1717-22. doi: 10.3892/or.2015.3747. Epub 2015 Jan 22.
The transcription factor, early growth response 1 (EGR1) belongs to the early growth response family. EGR1 regulates the transactivation of genes involved in growth inhibition and apoptosis by ionizing radiation. The aims of the present study were to evaluate the expression of EGR1, and its relationship to prognosis, in patients with advanced laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) receiving chemoradiation therapy, and to observe the effect of EGR1 on the apoptosis of head and neck squamous cell carcinoma (HNSCC) cells treated with ionizing radiation. Expression of the EGR1 protein in tissue samples from patients with LHSCC was detected by immunohistochemistry. A high expression of the EGR1 protein was observed in 37 (67.3%) of the 55 LHSCC tissue samples examined. A high EGR1 protein expression in patients with LHSCC who were treated with chemoradiation was significantly associated with improved larynx-preservation survival (p=0.04). The 5-year disease-specific survival rate with larynx preservation was 59% in patients with a high EGR1 protein expression vs. 30% in those with a low EGR1 protein expression. In the human HNSCC cell line, PCI50, EGR1 mRNA expression was induced at 30-60 min, and EGR1 protein expression was induced at 60-120 min, after exposure to a 5 Gy dose of ionizing radiation. To evaluate the impact of EGR1 on radiation-induced apoptosis, we used small‑interfering RNA to knock down endogenous EGR1 gene expression. Cleaved caspase 3, cleaved caspase 7, and cleaved PARP were decreased, while XIAP was increased, in EGR1-knockdown PCI50 cells compared to negative control PCI50 cells, at all observed post-irradiation time points. These findings suggested that EGR1 knockdown inhibits radiation-induced apoptosis. In conclusion, EGR1 may be associated with larynx-preservation survival, through the regulation of radiation-induced apoptosis in patients with LHSCC treated with chemoradiation. Although further investigations are required to support the present study, EGR1 serves as a favorable biomarker of radiosensitivity in the treatment of LHSCC.
转录因子早期生长反应1（EGR1）属于早期生长反应家族。EGR1通过电离辐射调节参与生长抑制和凋亡的基因的反式激活。本研究的目的是评估接受放化疗的晚期喉和下咽鳞状细胞癌（LHSCC）患者中EGR1的表达及其与预后的关系，并观察EGR1对接受电离辐射治疗的头颈部鳞状细胞癌（HNSCC）细胞凋亡的影响。采用免疫组织化学法检测LHSCC患者组织样本中EGR1蛋白的表达。在55例接受检测的LHSCC组织样本中，37例（67.3%）观察到EGR1蛋白高表达。接受放化疗的LHSCC患者中EGR1蛋白高表达与喉保留生存率提高显著相关（p=0.04）。EGR1蛋白高表达患者的5年喉保留疾病特异性生存率为59%，而EGR1蛋白低表达患者为30%。在人HNSCC细胞系PCI50中，暴露于5 Gy剂量的电离辐射后，EGR1 mRNA表达在30 - 60分钟被诱导，EGR1蛋白表达在60 - 120分钟被诱导。为了评估EGR1对辐射诱导凋亡的影响，我们使用小干扰RNA敲低内源性EGR1基因表达。在所有观察到的照射后时间点，与阴性对照PCI50细胞相比，EGR1敲低的PCI50细胞中裂解的半胱天冬酶3、裂解的半胱天冬酶7和裂解的聚（ADP-核糖）聚合酶减少，而X连锁凋亡抑制蛋白增加。这些发现表明EGR1敲低抑制辐射诱导的凋亡。总之，EGR1可能通过调节接受放化疗的LHSCC患者的辐射诱导凋亡与喉保留生存相关。尽管需要进一步研究来支持本研究，但EGR1在LHSCC治疗中作为放射敏感性的良好生物标志物。
