Wnt signaling pathway is essential for development and tumorigenesis,however,this signaling pathway in the progress of hepatocellular carcinoma (HCC) remains unclear. In this paper,we studied the function of human T-c...Wnt signaling pathway is essential for development and tumorigenesis,however,this signaling pathway in the progress of hepatocellular carcinoma (HCC) remains unclear. In this paper,we studied the function of human T-cell transcription factor-4 (TCF4),a key factor of Wnt signaling pathway,on the proliferation of HCC cell line. We showed that the expression of TCF4 mRNA in HCC cell line BEL-7402 was higher than that in immortalized normal liver cell line L02. Blockage of Wnt pathway by △NTCF4,a dominant negative TCF4,could suppress BEL-7402 cells growth and decrease the expression of cyclin D1 and c-myc,two of target genes of Wnt pathway. On the other hand,stimulating Wnt pathway by introducing a degradation-resistant β-catenin S37A could increase BEL-7402 cells proliferation. But all the treatments had no effect on L02 cells. Our data indicated that TCF4 might be another key factor in Wnt pathway involved in HCC cells proliferation and TCF4 could be an effective therapeutic target for suppressing the growth of hepatocellular cancers.展开更多
Objective： To investigate the expressions of E-cadherin, β-catenin, transcription factor 4 （TCF4）, which are related with Wnt/β-catenin signaling pathway, and Caudal-type Homeobox Protein 2 （CDX2） originated fr...Objective： To investigate the expressions of E-cadherin, β-catenin, transcription factor 4 （TCF4）, which are related with Wnt/β-catenin signaling pathway, and Caudal-type Homeobox Protein 2 （CDX2） originated from intestine, in various gastric diseases and its influence on gastric carcinogenesis and differentiation. Methods： A total of 319 various gastric diseases samples from gastroscopy were detected in situ using immunohistochemistry, and data were analyzed with Х^2 test and Kendall＇s tau-b rank correlation coefficient analysis. Results： Along with the progression from superficial gastritis （SG） to atrophic gastritis （AG） to gastric cancer （GC）, the expressions of E-cadherin and β-catenin appeared a decreasing tendency in total, while β-catenin emerged a decreasing tendency in the cell membrane and an increasing in the nucleus, and the highly positive expression rate of intranuclear transcription factor TCF4 appeared an increasing tendency. The transcription factor CDX2 had a higher expression in AG and GC than that in SG. The expression rates of the four proteins above in intestinal type adenocarcinoma were all higher than those in diffuse type carcinoma. There were positive correlations between E-cadherin and β-catenin expressed in cytoplasm, between β-catenin expressed in cell membrane and β-catenin in cytoplasm, between β-catenin expressed in cytoplasm and β-catenin in nucleus, between β-catenin and TCF4 in nucleus, between TCF4 and CDX2 in nucleus, respectively （P〈0.05）. And β-catenin and CDX2 had no relevance in nucleus （P〉0.05）. Conclusion： We found that the four proteins were involved in gastric carcinogenesis and the differentiation to intestinal type adenocarcinoma.展开更多
基金supported by Natural Science Fund of Jiangsu Province 2000SWX000B501.
文摘Wnt signaling pathway is essential for development and tumorigenesis,however,this signaling pathway in the progress of hepatocellular carcinoma (HCC) remains unclear. In this paper,we studied the function of human T-cell transcription factor-4 (TCF4),a key factor of Wnt signaling pathway,on the proliferation of HCC cell line. We showed that the expression of TCF4 mRNA in HCC cell line BEL-7402 was higher than that in immortalized normal liver cell line L02. Blockage of Wnt pathway by △NTCF4,a dominant negative TCF4,could suppress BEL-7402 cells growth and decrease the expression of cyclin D1 and c-myc,two of target genes of Wnt pathway. On the other hand,stimulating Wnt pathway by introducing a degradation-resistant β-catenin S37A could increase BEL-7402 cells proliferation. But all the treatments had no effect on L02 cells. Our data indicated that TCF4 might be another key factor in Wnt pathway involved in HCC cells proliferation and TCF4 could be an effective therapeutic target for suppressing the growth of hepatocellular cancers.
基金supported by the Technology Project of Liaoning Province (No. 2007225001-1)
文摘Objective： To investigate the expressions of E-cadherin, β-catenin, transcription factor 4 （TCF4）, which are related with Wnt/β-catenin signaling pathway, and Caudal-type Homeobox Protein 2 （CDX2） originated from intestine, in various gastric diseases and its influence on gastric carcinogenesis and differentiation. Methods： A total of 319 various gastric diseases samples from gastroscopy were detected in situ using immunohistochemistry, and data were analyzed with Х^2 test and Kendall＇s tau-b rank correlation coefficient analysis. Results： Along with the progression from superficial gastritis （SG） to atrophic gastritis （AG） to gastric cancer （GC）, the expressions of E-cadherin and β-catenin appeared a decreasing tendency in total, while β-catenin emerged a decreasing tendency in the cell membrane and an increasing in the nucleus, and the highly positive expression rate of intranuclear transcription factor TCF4 appeared an increasing tendency. The transcription factor CDX2 had a higher expression in AG and GC than that in SG. The expression rates of the four proteins above in intestinal type adenocarcinoma were all higher than those in diffuse type carcinoma. There were positive correlations between E-cadherin and β-catenin expressed in cytoplasm, between β-catenin expressed in cell membrane and β-catenin in cytoplasm, between β-catenin expressed in cytoplasm and β-catenin in nucleus, between β-catenin and TCF4 in nucleus, between TCF4 and CDX2 in nucleus, respectively （P〈0.05）. And β-catenin and CDX2 had no relevance in nucleus （P〉0.05）. Conclusion： We found that the four proteins were involved in gastric carcinogenesis and the differentiation to intestinal type adenocarcinoma.
