Protein expression and significance of survivin and NF-κB in hepatocellular carcinoma
To detect the protein expressions of survivin and NF (nuclear factor)-κB and investigate their roles in the pathogenesis of hepatocellular carcinoma. A total of 206 cases were diagnosed as hepatocellular carcinoma, and immunohistochemical technique was used to detect the protein expressions of survivin and NF-κB in hepatocellular carcinoma samples and normal liver tissue specimens. Statistical analysis was performed to analyze the relationship of protein expressions of survivin and NF-κB and clinico-pathological parameters and prognosis. The expression of survivin was predominant in cytoplasm while that of NF-κB was in nucleolus. The positive rate of survivin protein was 78.2% in hepatocellular carcinoma and that of NF-κB was 81.1%. The positive rate of survivin and NF-κB was higher in hepatocellular carcinoma than that in benign hepatic tissue (11.7% and 15.5%). Significant differences existed in the expressions of survivin and NF-κB between hepatocellular carcinoma and normal hepatic tissue (P < 0.01). The expression of survivin was related to amicula invasion, portal vein tumor thrombus, lymph node metastasis and clinical stage in hepatocellular carcinoma (P < 0.01). The expression of NF-κB was also related to portal vein tumor thrombus, lymph node metastasis and clinical stage in hepatocellular carcinoma (P < 0.05). There was an obviously positive correlation between the expressions of survivin and NF-κB in hepatocellular carcinoma (r = 0.52, P < 0.01). Survival rate of patients for 1, 3 year of positive expression of survivin and NF-κB in hepatocellular carcinoma was 70.3% and 30.4%, respectively. And it was obviously lower than that of those of negative expression (88.5% and 61.5%). There was significant difference in the expressions of survivin and NF-κB between positive and negative subjects in 1, 3 year (P < 0.05). Protein expressions of survivin and NF-κB are higher in hepatocellular carcinoma. And they play mutually promoting roles in the development of hepatocellular carcinoma. Thus, an important prognostic indicator may be adopted.
[Show abstract] [Hide abstract] ABSTRACT: Canine histiocytic sarcoma (CHS) is an aggressive malignant neoplasm that originates from histiocytic lineage cells, including dendritic cells and macrophages, and is characterized by progressive local infiltration and a very high metastatic potential. Survivin is as an apoptotic inhibitory factor that has major functions in cell proliferation, including inhibition of apoptosis and regulation of cell division, and is expressed in most types of human and canine malignant neoplasms, including melanoma and osteosarcoma. To investigate whether survivin was expressed at high levels in CHS and whether its expression was correlated with the aggressive biological behavior of CHS, we assessed relation between survivin expression and CHS progression, as well as the effects of survivin inhibition on the biological activities of CHS cells. We comparatively analyzed the expression of 6 selected anti-apoptotic genes, including survivin, in specimens from 30 dogs with histiocytic sarcoma and performed annexin V staining to evaluate apoptosis, methylthiazole tetrazolium assays to assess cell viability and chemosensitivity, and latex bead assays to measure changes in phagocytic activities in 4 CHS cell lines and normal canine fibroblasts transfected with survivin siRNA. Survivin gene expression levels in 30 specimens were significantly higher than those of the other 6 genes. After transfection with survivin siRNA, apoptosis, cell growth inhibition, enhanced chemosensitivity, and weakened phagocytic activities were observed in all CHS cell lines. In contrast, normal canine fibroblasts were not significantly affected by survivin knockdown. These results suggested that survivin expression may mediate the aggressive biological activities of CHS and that survivin may be an effective therapeutic target for the treatment of CHS.0Comments 6Citations
- "Some groups have also suggested that survivin-mediated transcription is associated with P-glycoprotein/MDR1 overexpression in human breast cancer cells [36,37]. Other groups have demonstrated that cell transfected with the survivin gene may exhibit enhanced activity of specificity protein 1 as a transcription factor , and overexpression of survivin may affect NF-kB activity in cancer cells via feedback control [39,40]. Activated specificity protein 1 and NF-kB induce the production of chemoresistance genes and proteins, including P-glycoprotein and ABC transporter41424344. "