Correlation of nuclear transcription factor κB with vimentin expression in autoimmune thyroiditis
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AimTo assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-κB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors.MethodsWe analyzed 31 one renal cell tumors – 22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-κB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples.ResultsCytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 ± 18.9 vs 3.3 ± 10 % tumors, P = 0.001) and the latter in non-CCRCC type (71.7 ± 23.2 vs 31.1 ± 22.1 % tumors, P < 0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P = 0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P = 0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P < 0.001). Nuclear and cytoplasmic staining of NF-κB/p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-κB/65 staining and VEGF staining of diffuse pattern (P = 0.026). Association between NF-κB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P = 0.039) but not for nuclear NFkB/p65 staining (P = 0.099).ConclusionHigher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-κB/65 activity. This indicates that both VEGF and NF-κB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma.
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Aim: To study the expression of adhesion markers (E-cadherin, β-catenin and vimentin) associated with epithelial-mesenchymal transition (EMT) and their role in progression of endometrial carcinoma (EC). Materials and Methods: Expression of E-cadherin, β-catenin and vimentin was studied immunohistochemically in the samples of surgical material of 55 EC patients stage I–III. The proliferation index was determined by flow cytometry. Results: In the group of vimentin-negative EC, tumors of low differentiation grade and deep invasion in myometrium as well as high expression of E-cadherin and β-catenin prevailed compared with the cases with high expression of vimentin. In addition, in EC with high expression of vimentin, an increase in the number of cells with expression of E-cadherin in the cytoplasm (78.9 ± 3.6%) and β-catenin with cytoplasmic-nuclear localization (73.7 ± 3.2%) was observed compared with these indices in vimentin-negative tumors (45.4 ± 4.2%, p < 0.001 and 54.5 ± 2.6%, respectively, p < 0.005), which may indicate EMT-associated changes in EC with high expression of vimentin. Conclusions: The progression of the endometrioid carcinoma may occur in the setting of various molecular changes, in particular, with decreased expression of E-cadherin and β-catenin and high expression of vimentin, or in the absence of vimentin, utilizing other mechanisms of regulation of proliferative and metastatic potential.
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Objective To investigate the expression of NF-κB and epithelial-mesenchymal transition (EMT) related markers E-cadherin and Vimentin proteins in human pancreatic cancer tissues and its relation with the malignant features. Methods The expression of NF-κB、E-cadherin and Vimentin proteins in 62 cases of pancreatic cancer tissues were detected by using immunohistochemistry and compared with the clinicopathological data of pancreatic cancer. Results The positive expression rate of NF-κB was 81% (50/62), Vimentin protein increased of expression was 61% (38/62), and E-cadherin protein loss of expression was 55 % (34/62) in pancreatic cancer. The positive expression rate of NF-κB was significantly related with the lymph node metastasis (x2=11.761, P＜0.05), distant metastasis (x2=9.225, P＜0.05), the absent expression of epithelial marker E-cadherin protein (r =0.352, P ＜0.05) and the positive expression of mesenchymal marker Vimentin protein (r=0.343, P ＜0.05), but there was no relation with the patients gender,age, tumor location, tumor type and tumor differentiation (P ＞0.05). In addition, the significant correlation of E-cadherin expression loss and Vimentin expression with tumor lymph node metastasis and distant metastasis was found (x 2= 6.914, 4.984, 7.753, 5.144, P ＜0.05). Conclusion The overexpression of NF-κB in pancreatic cancer may accelerate invasion and metastasis of pancreatic cancer through inducing EMT.
Key words:
Pancreatic neoplasms; Immunohistochemistry; NF-kappa B; Epithelial cells; Cell transformation, neoplastic
CA19-9
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The oral squamous cell carcinoma (OSCC) is a leading cause of death in human malignancies. The aim of this study is to integrate the CAM Assay as a reliable and good working in vivo model for the evaluation of OSCC tumor samples and its growth into the clinical work flow.Fresh human Tumor samples (OSCCs) 1×1 cm in size were cut into 350-450μm thick slices by a Vibratome and put on the prepared CAM model.After growth of the tumor tissue on the CAM, we started with topical induction of proinflammatory cytokines (TNFα) and growth factors (TGFβ). After further growth of the tumor on the assay, we explanted the tumor tissue and first performed microscopic and then immunohistochemical examinations. E-cadherin and vimentin were used as Epithelial-to-mesenchymal transition (EMT) -makers and the histologic preparations were evaluated histomorphometrically. The results were correlated with clinical parameters of the patients.Under TNFα, the small tumors (T1 / T2) show higher E-cadherin expression than larger tumors (T3 / T4). The vimentin expression under TNFα behaved in the opposite direction, at T1 / T2 the expression decreased in T3 / T4 increased. Furthermore, an increased E-cadherin expression in N0 and diminished E-cadherin expression in N1 / N2b patients could be detected depending on the N-stage of the patients. Vimentin, on the other hand, was reduced in the N0 group and expressed more frequently in the N1 / N2b group. TGFβ induction also led to increased expression of vimentin in the T3 / T4 tumors and N1 / N2b stages.By integrating a CAM assay into the clinical workflow, tumors with preserved tumor architecture can be cultured and subjected to histological and molecular biology studies. Effects on biological behavior are recognizable and demonstrable in this model. The key markers E-cadherin and vimentin alone are not sufficient to represent the complexity of the EMT in this model. Further molecular biology and signaling pathway analyzes are necessary.
Proinflammatory cytokine
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Objective
To observer the effect of phosphatidylinositol-5 (GPC5) on epithelial-mesenchymal transition (EMT) in lung adenocarcinoma cells and to investigate the clinical correlation between the expression of GPC5 and EMT key proteins (E-cadherin, Twist1, Vimentin, N-cadherin) in human lung adenocarcinoma tissues.
Methods
Luciferase labeled lentivirus-induced GPC5 over-expression was used for in vitro studies in A549 cell line (OE-GPC5) and a negative control group (NC). Western blotting was used to compare the expression level differences in EMT related proteins between the two groups. Immunofluorescent assay was used to detect the expression of E-cadherin and Vimentin in the two groups under the intervention of EMT-induced factor transforming growth factor-β (TGF-β) (10 ng/ml, 36 h). The mRNA expression levels of GPC5, E-cadherin and Vimentin were detected by real-time quantitative PCR in 134 cases of lung adenocarcinoma tissues. The correlation analysis of clinical expression was performed by Pearson method.
Results
The expression level of E-cadherin in the A549 cell line was up-regulated by over-expressed GPC5 (P=0.008), and the expression levels of Vimentin (P=0.012), N-cadherin (P=0.001) and Twist1 (P=0.001) were down-regulated. The immunofluorescent assay indicated that the E-cadherin green fluorescence intensity in OE-GPC5 group was significantly stronger than in NC group (P=0.020), and the Vimentin green fluorescence intensity in OE-GPC5 group was significantly weaker than in NC group (P=0.001). Pearson correlation analysis showed that the mRNA expression of GPC5 was positively correlated with that of E-cadherin in human lung adenocarcinoma tissues (P=0.007), and negatively with that of Twist1 (P=0.023).
Conclusion
GPC5 may play a role of tumor suppressor gene by reversing the EMT process of lung adenocarcinoma.
Key words:
Phosphatidylinositol-5; Epithelial-mesenchymal transition; Lung adenocarcinoma
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To investigate the kinetic expression and alteration of nuclear transcription factor-kappa B (NF-kappaB) and its gene in hepatocellular carcinoma (HCC) development.A hepatoma model was established with N-(2-fluorenyl) acetamide (2-FAA) using male SD rats. Morphological changes and dynamic alterations of NF-kappaB and NF-kappaB mRNA of the rat livers at different stages of HCC development were observed by pathological examinations. The liver specimens from HCC patients were collected by self-control method. The expression of NF-kappaB was quantitatively analyzed by ELISA.Hepatocytes showed vacuole-like denaturation, atypical hyperplasia, and transformation into highly differentiated cancerous hepatocytes with increasing tendencies of liver NF-kappaB and NF-kappaB mRNA expressions. The NF-kappaB positive material was granule-like and stained brown, with dot-nest-like staining localized in the nuclei and cytoplasm of HCC cells, but only in the cytoplasm of the cells of park cancer tissues. Its expression in HCC cells was stronger than that in their surrounding tissues (chi2 = 13.1, P less than 0.01). No positive relationship was found between NF-kappaB expression and histological grades, the number of tumors, or size of the tumors.The expression of NF-kappaB and its gene are associated with the development of HCC. To inhibit the expression may be useful to HCC therapy.
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Objective: To investigate the expressions of uPA and vimentin protein in hepatocellular carcinoma(HCC) and their clinicopathologic signi cance.Methods: e expressions of uPA and vimentin protein in HCC along with their paired adjacent tissues(88 cases) and normal liver tissues(8 cases) were determined by immumohistochemical staining.e relations of the expressions of the both proteins with the clinicopathologic characteristics of HCC patients,and the correlation between themselves were analyzed.Results: The positive expression rates of uPA and vimentin protein in HCC tissues were 63.6% and 72.7% respectively,and both were signi cantly higher than those in their adjacent tissues(27.3% and 15.9%) and normal liver tissue(12.5% and 12.5%)(all P0.0125).e expressions of uPA and vimentin protein in HCC were associated with the presence of portal vein tumor thrombus and liver capsule invasion(all P0.05),and there was a positive correlation between the expressions of uPA and vimentin protein in HCC tissues(r=0.227,P=0.034).Conclusion: e expressions of uPA and vimentin protein in HCC are positively correlated and both positive expressions are associated with the unfavorable clinical characteristics of the patients.
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Objective To study the roles of cytokeratin-19 ( CK-19 ),vimentin,vascular endothelial growth factor-C( VEGF-C ),and cyclooxygenase-2 ( COX-2 ) played in the occurrence and development of Graves'disease(GD) and Hashimoto's thyroiditis(HT).Methods 57 cases of GD and 58 cases of HT were enrolled in our study.Immunohistochemistry using SP method was carried out for assessment of the expression of CK-19,vimentin,VEGF-C,and COX-2 in the thyroid tissues.Results CK-19,VEGF-C,and COX-2 were expressed in the cytoplasm of thyroid follicular epithelial cells.Vimentin was expressed both in the mesenchyma and in the cytoplasm of thyroid follicular epithelial cells.The positive rates and expression intensities of CK-19 and VEGF-C in HT ( 86.2％,96.6％ ) were significantly higher than those in GD ( 43.9％,56.1％,all P＜0.05 ).The expression intensities of vimentin and COX-2 in GD ( 100.0％,93.1％ ) were similar to those in HT ( 100.0％,91.2 ％ ),while the expression intensity of COX-2 in HT was significantly higher than that in GD( all P＜0.05 ).The positive rates of CK-1 9 were much higher in type Ⅲ ( 81.3％ ) of GD than in type Ⅰ ( 1 5.8％ ) and type Ⅱ ( 40.9％ ) of GD,and also higher in type P( 100％ ) of HT than in type L(66.7％ ) of HT.The positive rates of VEGF-C were much higher in type Ⅲ ( 87.5％ ) of GD than in type Ⅰ ( 36.8％ ) and type Ⅱ ( 50.0％,all P ＜ 0.05 ) of GD.Conclusion Immunohistochemical detection of the expression of CK-19,vimentin,VEGF-C,and COX-2 may carry clinical significance in revealing the occurrence and development as well as evaluating the prognosis of Graves'disease and Hashimoto's thyroiditis.
Key words:
Graves' disease; Hashimoto's thyroiditis; Cytokeratin-19; Vimentin; Vascular endothelial grouth factor-C; Cyclooxygenase-2
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The vimentin gene is a hallmark of epithelial-to-mesenchymal transition and has been observed to be overexpressed in various types of tumor cell line and tissue. Previous studies have reported correlations between vimentin DNA methylation levels and subsequent vimentin expression levels in solid tumors, including breast and colorectal cancer; however, to the best of our knowledge, such a correlation has not been reported for gastric cancer (GC) using Lauren classification. Therefore, the present study aimed to quantify DNA methylation levels of the vimentin gene using quantitative (q) methylation-specific polymerase chain reaction (PCR) in intestinal-type GC cell lines (MKN-28, AGS and MKN-1), diffuse-type GC cell lines (SGC-7901, SNU-5 and KATO III), the GES-1 immortalized human non-neoplastic gastric epithelial cell line, as well as in tumor and paratumor normal tissue samples. Furthermore, the present study analyzed the messenger RNA expression of the vimentin gene in these cell lines and tissues by reverse transcription-qPCR. A comparison of the clinicopathological features was conducted between patients, grouped according to the Lauren classification. The present study identified that the vimentin promoter region was hypermethylated in all GC cell lines and tumor tissue samples when compared with immortalized normal gastric epithelial cells and paratumor normal tissues. In addition, vimentin promoter methylation levels were observed to be higher in intestinal-type cell lines when compared with those of diffuse-type lines and tissues. Correspondingly, vimentin expression levels were lower in intestinal-type gastric cell lines compared with those of diffuse-type cell lines and tissues, and were lowest in the non-neoplastic gastric cell line and paratumor normal tissues. Patients with diffuse-type GC were on average younger (P=0.023), and exhibited higher tumor (P=0.020), node (P=0.032) and TNM classification of malignant tumor stage (P=0.039) than those with intestinal-type GC. Following treatment of AGS cells (which demonstrated the highest methylation level of the vimentin gene) with 5-aza-2'-deoxycytidine, vimentin expression was restored significantly. Thus, the present study revealed that vimentin promoter methylation levels are inversely correlated with vimentin expression levels in GC (according to Lauren classification). High levels of methylation in the vimentin gene promoter region may be involved in carcinogenesis and the development of GC, and may provide a novel molecular classification for GC.
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Our previous in vivo experiment (paper has been published) has confirmed Feiyanning's regulation effect on epithelial cell markers Alpha-catenin, beta-catenin, E-Cadherin and mesenchymal cell markers N-cadherin, Fibronectin, vimentin. Based on previous study, the objective of this study is to further investigate the expression of epithelial-mesenchymal cell marker gene and protein intervened by Feiyanning in highly metastatic lung cancer cells 95-D in vitro.Human highly metastatic lung cancer 95-D cells were treated with different concentrations of Feiyanning in vitro, and then Real-time PCR and Western blot methods were used to detect mRNA and protein expression of epithelial-mesenchymal cell marker factor Alpha-catenin, beta-catenin, E-Cadherin, N-cadherin, Fibronectin and vimentin.Real-time PCR results showed that compared with the control group, Feiyanning at 20% concentration remarkably up-regulated the expression of Alpha-catenin (P<0.05), Feiyanning at 20% and 25% concentrations remarkably up-regulated the expression of E-Cadherin (P<0.05, P<0.01), Feiyanning had no significantly effect on beta-catenin at any concentration, 5% and 10% Feiyanning at 5% and 10% concentrations significantly dow-regulated the expression of mesenchymal cell marker vimentin factor (P<0.01), Feiyanning had no regulatory role on N-cadherin and Fibronectin at any concentration. Western blot results showed that Feiyanning at 5%, 10%, 15%, 20% and 25% concentrations significantly increased E-Cadherin protein expression (P<0.01), but had no regulation effect on Alpha-catenin and beta-catenin protein expression; Feiyanning at 5% and 10% concentrations had a down-regulation effect on N-cadherin and Fibronectin protein expression (P<0.01), and had no regulation effect on vimentin protein expression.Feiyanning play a role in inhibiting the adhesion of tumor heterogeneity and the athletic ability by regulating epithelial-mesenchymal cell marker factor expression, and thus inhibit the invasion and metastasis of lung cancer.
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