PMID- 21821462 OWN - NLM STAT- MEDLINE DCOM- 20120120 LR - 20220408 IS - 1879-0593 (Electronic) IS - 1368-8375 (Linking) VI - 47 IP - 10 DP - 2011 Oct TI - TRB3 overexpression due to endoplasmic reticulum stress inhibits AKT kinase activation of tongue squamous cell carcinoma. PG - 934-9 LID - 10.1016/j.oraloncology.2011.06.512 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Zhang, Jing AU - Zhang J AD - Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China. FAU - Wen, Hao-jie AU - Wen HJ FAU - Guo, Zhu-ming AU - Guo ZM FAU - Zeng, Mu-sheng AU - Zeng MS FAU - Li, Man-zhi AU - Li MZ FAU - Jiang, Yu-e AU - Jiang YE FAU - He, Xiao-guang AU - He XG FAU - Sun, Chuan-zheng AU - Sun CZ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110806 PL - England TA - Oral Oncol JT - Oral oncology JID - 9709118 RN - 0 (Antiviral Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (Cell Cycle Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (RNA, Small Interfering) RN - 0 (Repressor Proteins) RN - 0 (TRIB3 protein, human) RN - 11089-65-9 (Tunicamycin) RN - 67526-95-8 (Thapsigargin) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Antiviral Agents/pharmacology MH - Biomarkers, Tumor MH - Blotting, Western MH - Carcinoma, Squamous Cell/*metabolism/pathology MH - Cell Cycle Proteins/genetics/*metabolism MH - Endoplasmic Reticulum Stress/*physiology MH - Enzyme Inhibitors/pharmacology MH - Female MH - Humans MH - Lymphatic Metastasis MH - Male MH - Middle Aged MH - Neoplasm Recurrence, Local/metabolism/pathology MH - Phosphorylation MH - Prognosis MH - Protein Serine-Threonine Kinases/genetics/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA, Small Interfering/antagonists & inhibitors MH - Repressor Proteins/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Thapsigargin/pharmacology MH - Tongue Neoplasms/*metabolism/pathology MH - Tunicamycin/pharmacology EDAT- 2011/08/09 06:00 MHDA- 2012/01/21 06:00 CRDT- 2011/08/09 06:00 PHST- 2011/04/25 00:00 [received] PHST- 2011/06/19 00:00 [revised] PHST- 2011/06/25 00:00 [accepted] PHST- 2011/08/09 06:00 [entrez] PHST- 2011/08/09 06:00 [pubmed] PHST- 2012/01/21 06:00 [medline] AID - S1368-8375(11)00753-6 [pii] AID - 10.1016/j.oraloncology.2011.06.512 [doi] PST - ppublish SO - Oral Oncol. 2011 Oct;47(10):934-9. doi: 10.1016/j.oraloncology.2011.06.512. Epub 2011 Aug 6.