TRB3 overexpression due to endoplasmic reticulum stress inhibits AKT kinase activation of tongue squamous cell carcinoma
TRB3 overexpression due to endoplasmic reticulum stress inhibits AKT kinase activation of tongue squamous cell carcinoma
复制标题
内质网应激引起的TRB3过表达抑制舌鳞状细胞癌AKT激酶激活
DOI：
10.1016/j.oraloncology.2011.06.512
复制
发表时间：
2011-10-01
期刊：
影响因子：
4.8
通讯作者：
Sun, Chuan-zheng
中科院分区：
文献类型：
--
作者：
Zhang, Jing;Wen, Hao-jie;Sun, Chuan-zheng
本研究旨在探讨内质网应激（ERS）诱导基因TRB 3在口腔舌鳞状细胞癌（OTSCC）中的意义及其与AKT的关系。采用RT-PCR、Western blot和免疫组化方法检测OTSCC组织及癌旁正常组织中TRB 3和磷酸化AKT（p-AKT）的表达。通过TRB 3腺病毒质粒（Ad-TRB 3）转染和短发夹RNA（shRNA）抑制验证TRB 3与AKT的相关性。RT-PCR检测18例OTSCC中15例TRB 3 mRNA表达明显高于癌旁组织（83.3%，P < 0.01）。Western blot检测18例OTSCC中13例（72.2%）TRB 3和AKT均呈高表达，与癌旁组织比较差异有显著性（P < 0.05）。TRB 3在49.2%（63/128）的病理组织和13.3%（4/30）的癌旁组织中表达明显增高（P < 0.01）。TRB 3过表达与肿瘤病理T分期、淋巴结转移及复发密切相关。此外，在毒胡萝卜素（TG）或衣霉素（TU）诱导的ERS下，Tca 8113和CAL-27细胞中TRB 3的mRNA和蛋白表达均增加。此外，当用OTSCC Tca 8113细胞横切Ad-TRB 3时，p-AKT蛋白的表达降低。然而，当TRB 3被TRB 3 shRNA抑制时，p-AKT蛋白的表达增加。TRB 3表达与OTSCC预后密切相关。在ERS下，TRB 3上调，导致OTSCC中AKT的活化受到抑制。(C)2011爱思唯尔有限公司版权所有。
Our investigation aims to evaluate the significance of TRB3, an endoplasmic reticulum stress (ERS)-inducible gene, and explore its relationship with AKT in oral tongue squamous cell carcinoma (OTSCC). Expression of TRB3 and phosphorylated AKT (p-AKT) in OTSCC tissues and adjacent normal tissues were assessed by RT-PCR, Western blot and immunohistochemistry assay. Correlation of TRB3 and AKT was validated by TRB3 adenovirus plasmid (Ad-TRB3) transfection and short hairpin RNA (shRNA) inhibition. The mRNA expression of TRB3 was significantly higher than adjacent noncancerous tissues by RT-PCR in 15 of 18 specimens of OTSCC (83.3%, P < 0.01). Both of TRB3 and AKT were highly expressed in 13 of 18 (72.2%) specimens of OTSCC comparing with adjacent noncancerous tissues by Western blot assay (P < 0.05). TRB3 was significantly elevated in 49.2% (63/128) of pathologically confirmed specimens and 13.3% (4/30) of adjacent noncancerous specimens by immunohistochemical analysis (P < 0.01). TRB3 overexpression was closely correlated with tumor pathological T stage, lymph node metastasis and tumor recurrence. In addition, both mRNA and protein expression of TRB3 was increased under thapsigargin (TG) or tunicmycin (TU)-induced ERS in Tca8113 and CAL-27 cells. Moreover, expression of p-AKT protein decreased when Ad-TRB3 was transected with OTSCC Tca8113 cells. However, expression of p-AKT protein increased when TRB3 was inhibited by TRB3 shRNA inhibition. TRB3 expression was closely correlated with OTSCC prognosis. Under ERS, TRB3 was up-regulated, resulting in inhibiting the activation of AKT in OTSCC. (C) 2011 Elsevier Ltd. All rights reserved.