AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageai carcinoma and adjacent normal tissues. METHODS: The expression of HSP70...AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageai carcinoma and adjacent normal tissues. METHODS: The expression of HSP70 and grp94 in 78 human esophageai cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis. RESULTS: Both esophageai cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageai carcinoma, 95.0%(72/78) showed positive HSP70, mainly stained in nuclei, while grp94 was mainly stained in cell plasma, and the positive rate was 71.8% (56/78).There was a significant difference in the expression of HSP70 and grp94 between esophageai cancer and adjacent normal tissues (P<0.01). Compared with adjacent normal tissues, there was a significant difference between differential types and HSP70 expression (P<0.01). CONCLUSION: HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70 is related to the differentiation of esophageai carcinoma.展开更多
The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morpholog...The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.展开更多
Objective： To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods： Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Pr...Objective： To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods： Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Protein expression was detected with immunohistochemical staining, mRNA expression levels of GRP78 and GRP94 were determined by semiquantitative reverse transcriptase polymerase chain reaction （RT-PCR） after mRNA extraction. Results： The expression of GRP94 and GRP78 was significantly higher in colon cancer when compared to those in colon adenoma and normal tissue （P〈0.01）. GRP94 mRNA and protein expression was found to be in close relationship with the grade of differentiation, Dukes stages, lymph node involvement and remote metastasis in colon cancer （P〈0.01）, but no relationship with gender and age （P〉0.05）. GRP78 mRNA and protein expression increased with cancer progression along the normal tissue-adenoma-cancer sequence, but showed no association with grade of differentiation, Dukes stages, lymph node involvement, remote metastasis, gender and age （P〉0.05）. The mRNA expression of GRP78 and GRP94 was consistent with the proteins （P〈0.01）, but there is no correlation between overexpression of GRP78 and GRP94 （P〉0.05）, and the patients with both strong GRP78 and GRP94 protein expression did not show advanced tumor stages （P〉0.05）. Conclusion： Overexpression of GRP78 and GRP94 was found in colon cancer. Overexpression of GRP94 was closely related to cellular differentiation, Dukes stages, invasion and metastasis.展开更多
N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 h...N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 hepatocarcinoma cells in previous study. In this study, cDNA array gene expression profiles were compared between GnT-V-AS/7721 and parental 7721 cells. The data indicated that GnT-V-AS/7721 showed a characteristic expression pattern consistent with the ER stress. The molecular mechanism of the ER stress was explored in GnT-V-AS/7721 by the analysis on key molecules in both two unfolded protein response （UPR） pathways. For ATF6 and Irel/XBP-1 pathway, it was evidenced by the up-regulation of BIP at mRNA and protein level, and the appearance of the spliced form ofXBP-1. As for PERK/eIF2α pathway, the activation of ER eIF2α kinase PERK was observed. To confirm the results from GriT-V-AS/7721 cells, the key molecules in the UPR were examined again in 7721 cells interfered with the GnT-V by the specific RNAi treatment. The results were similar with those from GnT-V-AS/7721, indicating that blocking of GnT-V can specifically activate ER stress in 7721 cells. Rate of 3H-Man incorporation corrected with rate of 3H-Leu incorporation in GnT-V-AS/7721 was down-regulated greatly compared with the control, which demonstrated the deficient function of the enzyme synthesizing N-glycans after GnT-V blocking. Moreover, the faster migrating form of chaperone GRP94 associated with the underglycosylation, and the extensively changed N-glycans structures of intracellular glycoproteins were also detected in GnT-V-AS/7721. These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo.展开更多
基金Supported by the Youth Research Scientific Foundation of Beijing (02-31)
文摘AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageai carcinoma and adjacent normal tissues. METHODS: The expression of HSP70 and grp94 in 78 human esophageai cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis. RESULTS: Both esophageai cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageai carcinoma, 95.0%(72/78) showed positive HSP70, mainly stained in nuclei, while grp94 was mainly stained in cell plasma, and the positive rate was 71.8% (56/78).There was a significant difference in the expression of HSP70 and grp94 between esophageai cancer and adjacent normal tissues (P<0.01). Compared with adjacent normal tissues, there was a significant difference between differential types and HSP70 expression (P<0.01). CONCLUSION: HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70 is related to the differentiation of esophageai carcinoma.
文摘The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.
基金supported by a grant from the Doctoral science Foundation of Liaoning Province (No.20041052)
文摘Objective： To investigate the expression of glucose regulated proteins GRP78 and GRP94 in human colon cancer. Methods： Tissues of resected primary colon cancer, colon adenoma and normal tissue were investigated. Protein expression was detected with immunohistochemical staining, mRNA expression levels of GRP78 and GRP94 were determined by semiquantitative reverse transcriptase polymerase chain reaction （RT-PCR） after mRNA extraction. Results： The expression of GRP94 and GRP78 was significantly higher in colon cancer when compared to those in colon adenoma and normal tissue （P〈0.01）. GRP94 mRNA and protein expression was found to be in close relationship with the grade of differentiation, Dukes stages, lymph node involvement and remote metastasis in colon cancer （P〈0.01）, but no relationship with gender and age （P〉0.05）. GRP78 mRNA and protein expression increased with cancer progression along the normal tissue-adenoma-cancer sequence, but showed no association with grade of differentiation, Dukes stages, lymph node involvement, remote metastasis, gender and age （P〉0.05）. The mRNA expression of GRP78 and GRP94 was consistent with the proteins （P〈0.01）, but there is no correlation between overexpression of GRP78 and GRP94 （P〉0.05）, and the patients with both strong GRP78 and GRP94 protein expression did not show advanced tumor stages （P〉0.05）. Conclusion： Overexpression of GRP78 and GRP94 was found in colon cancer. Overexpression of GRP94 was closely related to cellular differentiation, Dukes stages, invasion and metastasis.
文摘N-acetylglucosaminyltransferase V （GnT-V） is an important tumorigenesis and metastasis-associated enzyme. To study its biofunction, the GnT-V stably suppressed cell line （GnT-V-AS/7721） was constructed from 7721 hepatocarcinoma cells in previous study. In this study, cDNA array gene expression profiles were compared between GnT-V-AS/7721 and parental 7721 cells. The data indicated that GnT-V-AS/7721 showed a characteristic expression pattern consistent with the ER stress. The molecular mechanism of the ER stress was explored in GnT-V-AS/7721 by the analysis on key molecules in both two unfolded protein response （UPR） pathways. For ATF6 and Irel/XBP-1 pathway, it was evidenced by the up-regulation of BIP at mRNA and protein level, and the appearance of the spliced form ofXBP-1. As for PERK/eIF2α pathway, the activation of ER eIF2α kinase PERK was observed. To confirm the results from GriT-V-AS/7721 cells, the key molecules in the UPR were examined again in 7721 cells interfered with the GnT-V by the specific RNAi treatment. The results were similar with those from GnT-V-AS/7721, indicating that blocking of GnT-V can specifically activate ER stress in 7721 cells. Rate of 3H-Man incorporation corrected with rate of 3H-Leu incorporation in GnT-V-AS/7721 was down-regulated greatly compared with the control, which demonstrated the deficient function of the enzyme synthesizing N-glycans after GnT-V blocking. Moreover, the faster migrating form of chaperone GRP94 associated with the underglycosylation, and the extensively changed N-glycans structures of intracellular glycoproteins were also detected in GnT-V-AS/7721. These results supported the mechanism that blocking of GnT-V expression impaired functions of chaperones and N-glycan-synthesizing enzymes, which caused UPR in vivo.
