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Objective To investigate the relationships between the expression levels of tumor necrosis factor receptor associated factor 4 (TRAF4) and ribosomal S6 protein kinase 4 (RSK4) protein in gastric cancer tissues and the recurrence after laparoscopic radical gastrectomy. Methods In total, 176 patients were divided into the recurrence and non-recurrence group, and the expression levels of TRAF4 and RSK4 protein in cancer and adjacent tissues and in gastric cancer tissues in the recurrence and non-recurrence group were compared. The influencing factor of recurrence and the efficacy of TRAF4 and RSK4 protein expression in predicting recurrence were analyzed. Results The positive expression rate of TRAF4 protein in gastric cancer tissues was higher than that in adjacent tissues (P < 0.05) and that in the recurrence group was higher than that in the non-recurrence group (P < 0.05). The positive expression rate of RSK4 protein in gastric cancer tissues was lower than that in adjacent tissues (P < 0.05) and that in the recurrence group was lower than that in non-recurrence group (P < 0.05). The largest tumor diameter 5 cm, poor differentiation, TNM Ⅲ stage, depth of invasion T3-T4, lymph node metastasis, absence of adjuvant chemotherapy after operation, positive expression of TRAF4 and RSK4 protein, and regular diet w influenced the post-operative recurrence (all P < 0.05). The accuracy of TRAF4 and RSK4 protein in gastric cancer tissues in combined predicting the recurrence was 83.52%. Conclusion The expression of TRAF4 protein is high, and the RSK4 protein is low in gastric cancer tissue, which are related to recurrence.
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Objective:To identify potential tumor markers for the development and recurrence of hepatocelullar carcinoma (HCC), this research studied the relationship between the expression of the tumor necrosis factor receptor-associated factor 4 (TRAF4) and tumor angiogenesis together with its survival time of HCC patients.Methods:The expressions of TRAF4, vascular endothelial growth factor and CD34 were performed upon 90 patients with curative liver resection between August 2006 and November 2009 by immunohistochemical method in locally advanced HCC and adjacent non-tumoral liver. The expression of TRAF4 was determined by the Spearman rank correlation. Their prognostic factors on disease free survival (DFS) and overall survival (OS) were guaranteed by Kaplan-Meier and Cox regression analyses. The detection of the levels of vascular endothelial growth factor and CD34 was fulfilled in 90 cases of HCC.Results:TRAF4 expression was both significantly higher in HCC than in surrounding non-tumor tissues (57.8% vs. 22.2 %; P<0.001) and significantly correlated with tumor size and tumor staging. High TRAF4 was correlated with reduced DFS rate (P=0.001) and overall OS rate (P<0.001) and were displayed in Kaplan-Meier survival analysis.Conclusions:TRAF4 is involved with multifarious clinicopathologic features. TRAF4 expression, as an independent adverse prognostic factor, DFS and OS in HCC, is associated with increased tumor angiogenesis. The combined detection of TRAF4 in locally advanced HCC is a trustworthy predictive factor for the tumor development and recurrence.
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Objective: To identify potential tumor markers for the development and recurrence of hepatocelullar carcinoma (HCC), this research studied the relationship between the expression of the tumor necrosis factor receptor-associated factor 4 (TRAF4) and tumor angiogenesis together with its survival time of HCC patients. Methods: The expressions of TRAF4, vascular endothelial growth factor and CD34 were performed upon 90 patients with curative liver resection between August 2006 and November 2009 by immunohistochemical method in locally advanced HCC and adjacent non-tumoral liver. The expression of TRAF4 was determined by the Spearman rank correlation. Their prognostic factors on disease free survival (DFS) and overall survival (OS) were guaranteed by Kaplan-Meier and Cox regression analyses. The detection of the levels of vascular endothelial growth factor and CD34 was fulfilled in 90 cases of HCC. Results: TRAF4 expression was both significantly higher in HCC than in surrounding non-tumor tissues (57.8% vs. 22.2 %; P<0.001) and significantly correlated with tumor size and tumor staging. High TRAF4 was correlated with reduced DFS rate (P=0.001) and overall OS rate (P<0.001) and were displayed in Kaplan-Meier survival analysis. Conclusions: TRAF4 is involved with multifarious clinicopathologic features. TRAF4 expression, as an independent adverse prognostic factor, DFS and OS in HCC, is associated with increased tumor angiogenesis. The combined detection of TRAF4 in locally advanced HCC is a trustworthy predictive factor for the tumor development and recurrence.
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Objective_To investigate whether overexpression of TRAF4 in human breast cancer may have impact on its cell proliferation.Methods_This study has two groups, MDA-MB-231 transfected with pcDNA3-TRAF4-DM-TRAF or pcDNA3 .We detected the expression and localization of TRAF4 with immunofluorescence and western blot.We detected the expression of the phosphorylation level of p70S6K and S6 with westernblot.Flow cytometry was used to detecte cell cycle.MTT Assay was used to detected cell reproductive capacity.Results_TRAF4 local-ized in both cytoplasm and nuclei in MDA-MB-231.Nuclear expression of TRAF4 in nuclei was lower than that in cytoplasm (P<0.05).After pcDNA3-TRAF4-DM-TRAF was transfected into the cells, the expression of TRAF4 in nuclei was increased (P<0.05).The phosphorylation level of p70S6K and S6 significantly increaseced (P<0.05,P<0.01).More S phase cells were recorded(P<0.01) by FCM.The cell proliferation was promoted by MTT ( P<0.01) .Conclusions_The expression of TRAF4 in nuclei may play an important role in the cell prolif-eratuion by promoting p70S6K and S6 activation.
ABSTRACT
TRAF4 is a unique member of TRAF family, which is essential for innate immune response, nervous system and other systems. In addition to be an adaptor protein, TRAF4 was identified as a regulator protein in recent studies. We have determined the crystal structure of TRAF domain of TRAF4 (residues 292-466) at 2.60 Å resolution by X-ray crystallography method. The trimericly assembled TRAF4 resembles a mushroom shape, containing a super helical "stalk" which is made of three right-handed intertwined α helixes and a C-terminal "cap", which is divided at residue L302 as a boundary. Similar to other TRAFs, both intermolecular hydrophobic interaction in super helical "stalk" and hydrogen bonds in "cap" regions contribute directly to the formation of TRAF4 trimer. However, differing from other TRAFs, there is an additional flexible loop (residues 421-426), which contains a previously identified phosphorylated site S426 exposing on the surface. This S426 was reported to be phosphorylated by IKKα which is the pre-requisite for TRAF4-NOD2 complex formation and thus to inhibit NOD2-induced NF-κB activation. Therefore, the crystal structure of TRAF4-TRAF is valuable for understanding its molecular basis for its special function and provides structural information for further studies.