TRB3 overexpression due to endoplasmic reticulum stress inhibits AKT kinase activation of tongue squamous cell carcinoma.

Autor: Zhang J; Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China., Wen HJ, Guo ZM, Zeng MS, Li MZ, Jiang YE, He XG, Sun CZ
Jazyk: angličtina
Zdroj: Oral oncology [Oral Oncol] 2011 Oct; Vol. 47 (10), pp. 934-9. Date of Electronic Publication: 2011 Aug 06.
DOI: 10.1016/j.oraloncology.2011.06.512
Abstrakt: 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.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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