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Objective To investigate the effects of specific methyltransferase inhibitor of 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the promoter methylation of E-cadherin (E-cad) gene, protein expression in human cervical cancer SiHa cells, and the cell biological behavior. Methods SiHa cells were treated with 5-Aza-CdR at different concentrations. Quantitative methylation-specific polymerase chain reaction (QMSP) was used to examine CpG island promoter methylation level of E-cad gene before and after treatment. The experimental group of the optimum concentration was selected. The expression levels of E-cad mRNA and its protein in SiHa cells line were detected by quantitative real-time polymerase chain reaction (RT-PCR) and western blot respectively. Cell adhesion test was used to measure cell adhesion ability and Transwell test was used to detect cell invasion and migration ability. Results E-cad gene promoter methylation index (PMR) of 5-Aza-CdR at 0, 1, 5, 10, 15 μmol/L level was (53.0 ±1.6) %, (50.0 ±1.2) %, (44.0 ±1.4) %, (27.0 ±1.7) %, (15.0±8.2) %respectively, and PMR value decreased gradually with the increase of 5-Aza-CdR concentration. Furthermore, PMR value was the lowest at 15μmol/L, and the difference was statistically significant compared with other 4 groups (P< 0.01). Then 5-Aza-CdR at 15 μmol/L was selected as the following experimental concentration. The expression of E-cad mRNA and its protein in the 5-Aza-CdR group were significantly higher than those in the blank control group (P<0.05). The rates of cell adhesion , cell invasion inhibition and migration inhibition were all increased with significant differences (P<0.05). Conclusions 5-Aza-CdR can upregulate E-cad mRNA and protein expression level in cervical cancer SiHa cells, reduce cell invasion and migration ability, and promote the adhesion of SiHa cells, which has reversed hypermethylation in the promoter region of E-cad gene partly.
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Objective To investigate the effects of specific methyltransferase inhibitor of 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the promoter methylation of E-cadherin (E-cad) gene, protein expression in human cervical cancer SiHa cells, and the cell biological behavior. Methods SiHa cells were treated with 5-Aza-CdR at different concentrations. Quantitative methylation-specific polymerase chain reaction (QMSP) was used to examine CpG island promoter methylation level of E-cad gene before and after treatment. The experimental group of the optimum concentration was selected. The expression levels of E-cad mRNA and its protein in SiHa cells line were detected by quantitative real-time polymerase chain reaction (RT-PCR) and western blot respectively. Cell adhesion test was used to measure cell adhesion ability and Transwell test was used to detect cell invasion and migration ability. Results E-cad gene promoter methylation index (PMR) of 5-Aza-CdR at 0, 1, 5, 10, 15 μmol/L level was (53.0 ±1.6) %, (50.0 ±1.2) %, (44.0 ±1.4) %, (27.0 ±1.7) %, (15.0±8.2) %respectively, and PMR value decreased gradually with the increase of 5-Aza-CdR concentration. Furthermore, PMR value was the lowest at 15μmol/L, and the difference was statistically significant compared with other 4 groups (P< 0.01). Then 5-Aza-CdR at 15 μmol/L was selected as the following experimental concentration. The expression of E-cad mRNA and its protein in the 5-Aza-CdR group were significantly higher than those in the blank control group (P<0.05). The rates of cell adhesion , cell invasion inhibition and migration inhibition were all increased with significant differences (P<0.05). Conclusions 5-Aza-CdR can upregulate E-cad mRNA and protein expression level in cervical cancer SiHa cells, reduce cell invasion and migration ability, and promote the adhesion of SiHa cells, which has reversed hypermethylation in the promoter region of E-cad gene partly.
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BACKGROUND/AIMS: Pregnancy-associated gastric cancer is a rare condition. This case-control study was performed to identify the clinicopathological features and prognostic factors of pregnancy-associated gastric cancer. METHODS: All consecutive patients who presented to our tertiary referral hospital with pregnancy-associated gastric cancer from 1991 to 2012 were identified. Two age-, sex-, and stage-matched controls for each case were also identified from the records. Clinicopathological, gynecological, and oncological outcomes were recorded. Immunohistochemical staining was performed for estrogen receptor, progesterone receptor, epidermal growth factor receptor, human epidermal growth factor receptor, and E-cadherin. Fluorescence in situ hybridization was performed for fibroblast growth factor receptor 2. RESULTS: The median overall survival rates of the pregnancy-associated gastric cancer and control groups were 7.0 months and 15.0 months, respectively (p=0.189). Poor prognostic factors included advanced stage and tumor location in the corpus or the entire stomach but not pregnancy status or loss of E-cadherin. Pregnancy-associated gastric cancer was associated with a longer time from diagnosis to treatment (21 days vs 7 days, p=0.021). The two groups did not differ in the expression of the receptors or E-cadherin. CONCLUSIONS: The dismal prognosis of pregnancy-associated gastric cancer may related to the tumor stage and location rather than to pregnancy itself.
Subject(s)
Humans , Pregnancy , Cadherins , Case-Control Studies , Diagnosis , Estrogens , Fluorescence , In Situ Hybridization , Prognosis , ErbB Receptors , Receptor, Fibroblast Growth Factor, Type 2 , Receptors, Progesterone , Stomach , Stomach Neoplasms , Survival Rate , Tertiary Care CentersABSTRACT
Invasion and migration are distinctive features of the malignant tumors.Studies showed that epithelial-mesenchymal transition ( EMT) , a conversion process with the loss of epithelial cell features and the gain of mesenchymal phenotype has been recog-nized as a key element of invasion and migration of malignancy.When EMT occurs, the downregulation of E-cadherins and the loss of adhesion in extracellular matrix play a critical role which are regarded as important indicators in the assessment of EMT.The latest re-searches indicated that integrin, one of the cell adhesion molecules family, was involved in EMT directly or indirectly through mediating either adhesion among cells, extracellular matrix or signal pathways by activating multiple kinases tyrosine phosphorylation cascade. The relationship between EMT and integrin is summarized in this article.
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The hereditary diffuse gastric cancer (HDGC) is associated with CDHI (E-cadherin gene)germline mutations, and accounts for about one-third of the familial gastric cancer (FGC) cases. The other two thirds FGC cases which are not fit the diagnosis standard of HDGC remain lack of clear molecular diagnosis basis. The current disposal of prophylactic gastrectomy in FGC according to E-cadherins genetic counseling, has clinical significance only in part of HDGC.
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Objective To investigate the expression and significance of S100A4 protein and Ecadherin in coloreetal carcinoma. Methods S-P immunohistochemical method was used to detect the expression of S100A4 and E-cadherin in 87cases with colorectal carcinoma and 87 cases with adjacent colorectal tissue, and the expression of S100A4 and E--cadherin were analyzed with relation to clinicopathologic factors and post-operative five-year survival. Results There was no expression for S100A4 protein in glandular epithelium of adjacent colorectal tissues. The positive expression rate of S100A4 was 64.4 %(56/87) in colorectal carcinoma. There was a significant difference between eolorectal carcinoma and adjacent group(P ＜0.01). The expression of S100A4 was positively correlated with the clinical stages, lymph node metastasis and five-year survival (P ＜0.05), but not with other clinicopathalagic factors (P ＞0.05). There was 100 % expression for E-cadherin in adjacent colorectal tissues. The positive expression rate of Ecadherin was 62.1%(54187) in colorectal carcinoma. There was a significant difference between colorectal carcinoma and adjacent group (P ＜0.01). The expression of E-cadherin was positively correlated with the clinical stages, lymph node metastasis, tumor site and five-year survival (P ＜0.05), hut not with other clinicopathologic factors (P ＞0.05). The expression of S100A4 was negatively correlated to E-cadherin in colorectal carcinoma without statistical meaning(r =-0.087, P ＞0.05). Conclusion S100A4 and E-cadherin are closely related with colorectal cancer invasion, metastasis and prognosis; S100A4 might be an important predictor of the clinicopathologic features and prognosis of eolorectal carcinoma.
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BACKGROUND/AIMS: Disruption of the cell-to-cell junction with changes in the expression of the junctional proteins is the hallmark of cancer invasion and metastasis. To investigate the roles of claudin-1, beta-catenin and E-cadherin in adenocarcinoma of the colon, the relationship of their expression with clinical and pathological factors were examined. METHODS: The expression of claudin-1, beta-catenin and E-cadherin were examined in 47 cases of adenocarcinoma of the colon by immunohistochemical staining. RESULTS: A reduced claudin-1 expression was associated with advanced lymph node metastasis (p=0.019) and histological dedifferentiation at the invasive front (p=0.030). A reduced expression of beta-catenin and E-cadherin were correlated with histological dedifferentiation (p=0.012, p=0.010, respectively). The reduced expression of two or more proteins was correlated with the histological findings of dedifferentiation (p=0.030). CONCLUSIONS: These results suggest that loss of claudin-1, beta-catenin and E-cadherin expression may be correlated with the progression of adenocarcinoma of the colon and associated with an advanced histological grade.
Subject(s)
Adenocarcinoma , beta Catenin , Cadherins , Claudin-1 , Colon , Lymph Nodes , Neoplasm Metastasis , ProteinsABSTRACT
Objective To discuss the effect of CO2 artificial pneumoperitoneum on the invasion of the endometrial cancer in nude mouse resulted from the transplantation of the cancer cells and its mechanism.Methods Thirty nude mice were divided into 3 groups based on the time in the CO2 pneumoperitoneum circumstance.Control group: the small intestine of the nude mouse was exposed in air for 5 min,and the cancer cells were injected into right lower quadrant after suture.The gas was depleted after 40 min.40 min group: CO2 gas was poured into abdominal cavity to form a 4 mmHg artificial pneumoperitoneum for 5 min before cancer cells were injected into right lower quadrant.The gas were depleted after 40 min.80 min group: CO2 gas was poured into abdominal cavity to form a 4 mmHg artificial pneumoperitoneum for 5 min before cancer cells were injected into right lower quadrant.The gas were depleted after 80 min.The time that each group took to form a solid tumor was recorded.Four weeks later,the transplantation tumors were taken out and sliced into frozen sections and paraffin-embedded sections.The expression of ?1-intergrin and E-cadherins was detected by IMF.Results The time taken to form the solid cancer was shorter in the 40 min group and 80 min group than in the control group,with more blood vessel found(P0.05).Conclusion The CO2 pneumoperitoneum could enhance the abilities of invasion and adhesion of endometrial cancer cells,which is associated with the expression changes of ?1-intergrin and E-cadherins in the cancer cells.