ABSTRACT
Objective To detect the association between rs4646999 polymorphisms in the promoter region of the c-Jun and the prognosis of sporadic colorectal cancer. Methods rs4646999-673C>T genetypes were deter-mined by Taqman-MGB probes in 436 colorectal cancer cases. The survival curve was analyzed by Kaplan-Meier analysis and Cox regression.Western blot was used to analyze the expression levels of c-Jun protein in different gen-otypes. Results Univariate analysis showed that the cumulative survival rate of patients with rs4646999TT geno-type was significantly higher than that of patients with CT and CC genotype. Multivariate Cox regression analysis showed that the differentiation,lymph node metastasis,distant metastasis,TNM stage and rs4646999 genetypes were prognostic factors.Compared with the carriers of TT genotype,CT/CC complex genotypes were associated with poor prognosis of colorectal cancer(P<0.05).Protein expression analysis showed that the expression of c-Jun pro-tein in CC genotype was increased.In contrast,the TT genotype was decreased.Conclusions This study provided the evidence that rs4646999-673C>T genetic variant in c-Jun promoter regions is associated with the poor survival prognosis of colorectal cancer,possibly by elevating the protein expression levels that appeared to up-regulate activ-ity of c-Jun thus tumorigenesis.
ABSTRACT
OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. .
Subject(s)
Animals , Mice , Rats , Endoplasmic Reticulum Stress , Fatty Acids/metabolism , Hepatocytes/physiology , Unfolded Protein Response , Acetylcysteine/metabolism , Cell Line, Tumor , Cells, Cultured , Glutathione/metabolism , Hepatocytes/metabolism , Oxidation-Reduction , Protein FoldingABSTRACT
Objective To establish a model of injury to primarily cultured spinal cord neurons,mimicking the neuronal injury after complete transactional spinal cord trauma,for the sake of exploring changes in expression of an immediately-early gene,c-jun,in central nervous system injury. Methods Spinal cords were removed form fetal Wistar rats at the 14th gestation day and the neurons were cultured for 10 to 12 days.Then,mechanical injury was applied to the neurons by making regular scores on the culture disk under direct vision with the aid of a self-made standard template.Morphology of the injured neurons and changes in expression of c-Jun protein were observed before and at different intervals after injury. Results c-Jun expression was noted in neuronal nuclei 10 min after injury and its peak appeared at 2 hrs.Besides,the density of positive neurons bore evidently an inverse proportion with their distance from the scores.Conclusion\ Positive expression in injury neurons show that c-jun gene enters the nucleoli of injured neurons and takes the role of “the third messenger” at early time after neuronal injury.