AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathologica...AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, α-catenin, β-catenin, γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS：The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression ratewas 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x^2=4.183 and x^2=5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (x^2=5.769, P<0.05). Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and inreduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.展开更多
AIM:To investigate whether abnormal expression of β-catenin in conjunction with overexpression of cyclinD1, c-myc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of...AIM:To investigate whether abnormal expression of β-catenin in conjunction with overexpression of cyclinD1, c-myc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of pancreatic cancer, and to analyze the relationship of β-catenin expression with cyclinDl, c-myc and MMP-7 expression. METHODS: Using immunohistochemistry,we examined the expression of β-catenin, cyclinD1,c-myc and MMP-7 in 47 pancreatic adenocarcinoma tissues, 12 pancreatic intraepithelial neoplasia (PanIN) and 10 normal pancreases, respectively. Proliferation cell nuclear antigen was also tested as the index of proliferative activity of pancreatic cancer cells. RESULTS: In 10 cases of normal pancreatic tissues, epithelial cells showed equally strong membranous expression of β-catenin protein at the cell-cell boundaries, but the expression of cyclinDl, c-myc and MMP-7 was negative. The expression of β-catenin, cyclinD1, c-myc and MMP-7 in PanIN and pancreatic adenocarcinoma tissues had no significant difference [6/12 and 32/47 (68.1%), 6/12 and 35/47 (74.5%), 5/12 and 33/47 (70.2%), 7/12 and 30/47 (63.8%), respectively]. The abnormal expression of β-catenin was significantly correlated to metastasis and one-year survival rate of pancreatic cancer, but had no relation with size, differentiation and cell proliferation. The expression of cyclinD1 was correlated with cell proliferation and extent of differentiation, but not with size, metastasis and one-year survival rate of the pancreatic cancer. The expression of c-myc was not correlated with size, extent of differentiation, metastasis and 1-year survival rate, but closely with cell proliferation of pancreatic cancer. The overexpression of MMP-7 was significantly associated with metastasis and 1-year survival rate of pancreatic cancer,but not with size, extent of differentiation and cell proliferation.There was a highly significant positive association between abnormal expression of β-catenin and overexpression of cyclinD1, c-myc and MMP-7 not only in PanIN (r= 1.000, 0.845, 0.845), but also in pancreatic cancer (r= 0.437, 0.452, 0.435). CONCLUSION: The abnormal expression of β-catenin plays a key role in the carcinogenesis and progression of human pancreatic carcinoma by up-regulating the expression of cyclinDl, c-myc and MMP-7, resulting in the degradation of extracellular matrix and uncontrolled cell proliferation and differentiation,β-catenin abnormal expression and MMP-7 overexpression may be considered as two useful markers for determining metastasis and prognosis of human pancreatic cancer.展开更多
AIM： To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS： Fifty-four SD rats were randomly divided into ischemic preconditioning gro...AIM： To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS： Fifty-four SD rats were randomly divided into ischemic preconditioning group （IP）, ischemia/ reperfusion group （IR） and sham operation group （SO）. The IP and IR groups were further divided into four sub-groups （n = 6）. Sham operation group （SO） served as the control group （n = 6）. A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. Alter 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinD1 mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration. RESULTS： Compared with IR group, IP group showed a significantly lower ALT level in 1h to 4h sub-groups （P 〈 0.05）. Proliferation index（PI） indicated by the S-phase and G2/M-phase ratio [（S＋G2/M）/（G0/G1＋S＋G2/M）] was significantly increased in IP group at 0 and 1 h （26.44 ± 7.60% vs 18.56 ± 6.40%,41.87 ± 7.27% vs 20.25 ± 6.70%, P 〈 0.05）. Meanwhile, cyclinD1 protein expression could be detected in IP group. But in IR group, cyclinD1 protein expression occurred 2 h alter reperfusion. The expression of cyclinD1 mRNA increased significantly in IP group at 0 and 1h （0.568 ± 0.112 vs 0.274 ± 0.069, 0.762 ± 0.164 vs 0.348 ± 0.093,P 〈 0.05）.CONCLUSION： Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.展开更多
Objective： To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods： High sensitive S-P immunohistochemical method was...Objective： To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods： High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results： Abnormal immunoreactivities of α- and β-catenins were observed in 37 （61.7%） and 42 （70%） cases of breast cancer tissues, respectively. There were 28 cases （46.7%） who showed cyclin D1 overexpression. The abnormal expression rates of α- and β-catenins in infiltrating Iobular carcinoma （ILC） were significantly higher than those in infiltrating ductal carcinoma （IDC） （P 〈 0.05）, but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer （P 〉 0.05）. The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer （P 〈 0.05）, but not with histological type and the extent of differentiation （P 〉 0.05）. Cyclin D1 overexpression was observed in 57.1% （24/42） of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% （4/18） of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 （r, = 0.321, P 〈 0.05）. Conclusion： The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α- and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.展开更多
AIM:To understand the role of P120ctn in E-cadherin-mediated cell-cell adhesion and signaling as well as inhepatoma cell biological function.METHODS:We stably overexpressed p120ctn isoform3A in BEL-7404 human hepatoma...AIM:To understand the role of P120ctn in E-cadherin-mediated cell-cell adhesion and signaling as well as inhepatoma cell biological function.METHODS:We stably overexpressed p120ctn isoform3A in BEL-7404 human hepatoma cells and studied theeffect of p120ctn on β-catenin and E-cadherin bindingas well as p120ctn and β-catenin subcellular localizationusing immunoprecipitation,Western blotting and confocalmicroscopy.We also investigated the inhibitory effectof p120ctn transfection on the expression of apoptoticprotein survivin survivin and cell cycle regulator cyclin D1in the cells.RERULTS:Western blotting indicated that p120ctnexpression increased after cells were transfected withp120ctn isoform 3A.The protein was located mainlyat membrane under immunofluorescent microscope.β-catenin nuclear expression was reduced afteroverexpression of p120ctn isoform 3A.The p120ctn-E-cadherin binding increased after transfection of p120ctnisoform 3A.Furthermore,overexpression of p120ctndown regulated the expression of apoptotic protein sur-vivin and cell cycle regulator cyclin D1.These effects ledto reduction of cell proliferation.CONCLUSION:Our results indicate that p120ctnplays an important role in regulating the formation ofE-cadherin and-catenin complex,cell apoptosis,cellcycle and cancer cell biological function.展开更多
Objective: To study cyclinD1/bcl-1 and p27/kip1 expression in gliomas and their correlation with pathological grade and prognosis. Methods: Immunohistochemical technique was used to detect the cyclinD1/bcl-1 and p...Objective: To study cyclinD1/bcl-1 and p27/kip1 expression in gliomas and their correlation with pathological grade and prognosis. Methods: Immunohistochemical technique was used to detect the cyclinD1/bcl-1 and p27/kip1 expression in 48 human brain glioma tissues of different malignant grades, and 12 normal non-neoplastic tissues collected from internal decompression. The data were analyzed quantitatively by the image system and also correlated retrospectively with the patients' clinical characteristics. Results: The immunohistochemical reaction for cyclinD1/bcl-1 and p27/kip1 was confined to the nuclei. The abnormal positive expression rates of both cyclinD1/bcl-1 and p27/kip1 in gliomas were found higher than that in non-neoplastic tissues(P<0.05). The number and staining intensity of cyclinD1/bcl-1 positive nuclei increased with malignant grades (P<0.05). On the contrary, the positive nuclei of p27/kip1 expression decreased in number and staining intensity with malignant grades(P<0.05). Higher expression of cyclinD1/bcl-1 or/and lower expression of p27/kip1 were associated with poor prognosis(P<0.05). Conclusion: The abnormal expression of both cyclinD1/bcl-1 and p27/kip1 might be closely related to the occurrence and development of gliomas and they might have synergistic effect. These data suggest that both cyclinD1/bcl-1 expression and p27/kip1 expression can act as an independent prognostic factor.展开更多
基金Supported by a grant of Shantou University Research & Development Fund,No.L03002
文摘AIM: To investigate the expression of E-cadherin, α-catenin,β-catenin, γ-catenin and cyclin D1 in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, α-catenin, β-catenin, γ-catenin and cyclin D1 was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS：The reduced expression rate of E-cadherin, α-catenin, β-catenin and γ-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression ratewas 56.5%. Expression of γ-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (x^2=4.183 and x^2=5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (x^2=5.769, P<0.05). Reduced expression of E-cadherin and γ-catenin was associated with poor differentiation of tumor, reduced expression of γ-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and γ-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and inreduced expression one and were 78% and 48% in γ-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of α-catenin correlated with that of E-cadherin and β-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and γ-catenin, but not α-catenin, β-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.
基金Supported by the Foundation of Shandong Education Committee,No. 03K02
文摘AIM:To investigate whether abnormal expression of β-catenin in conjunction with overexpression of cyclinD1, c-myc and matrix metalloproteinase-7 (MMP-7) correlated with the carcinogenesis, metastasis and prognosis of pancreatic cancer, and to analyze the relationship of β-catenin expression with cyclinDl, c-myc and MMP-7 expression. METHODS: Using immunohistochemistry,we examined the expression of β-catenin, cyclinD1,c-myc and MMP-7 in 47 pancreatic adenocarcinoma tissues, 12 pancreatic intraepithelial neoplasia (PanIN) and 10 normal pancreases, respectively. Proliferation cell nuclear antigen was also tested as the index of proliferative activity of pancreatic cancer cells. RESULTS: In 10 cases of normal pancreatic tissues, epithelial cells showed equally strong membranous expression of β-catenin protein at the cell-cell boundaries, but the expression of cyclinDl, c-myc and MMP-7 was negative. The expression of β-catenin, cyclinD1, c-myc and MMP-7 in PanIN and pancreatic adenocarcinoma tissues had no significant difference [6/12 and 32/47 (68.1%), 6/12 and 35/47 (74.5%), 5/12 and 33/47 (70.2%), 7/12 and 30/47 (63.8%), respectively]. The abnormal expression of β-catenin was significantly correlated to metastasis and one-year survival rate of pancreatic cancer, but had no relation with size, differentiation and cell proliferation. The expression of cyclinD1 was correlated with cell proliferation and extent of differentiation, but not with size, metastasis and one-year survival rate of the pancreatic cancer. The expression of c-myc was not correlated with size, extent of differentiation, metastasis and 1-year survival rate, but closely with cell proliferation of pancreatic cancer. The overexpression of MMP-7 was significantly associated with metastasis and 1-year survival rate of pancreatic cancer,but not with size, extent of differentiation and cell proliferation.There was a highly significant positive association between abnormal expression of β-catenin and overexpression of cyclinD1, c-myc and MMP-7 not only in PanIN (r= 1.000, 0.845, 0.845), but also in pancreatic cancer (r= 0.437, 0.452, 0.435). CONCLUSION: The abnormal expression of β-catenin plays a key role in the carcinogenesis and progression of human pancreatic carcinoma by up-regulating the expression of cyclinDl, c-myc and MMP-7, resulting in the degradation of extracellular matrix and uncontrolled cell proliferation and differentiation,β-catenin abnormal expression and MMP-7 overexpression may be considered as two useful markers for determining metastasis and prognosis of human pancreatic cancer.
基金Supported by Youth Foundation of Health Bureau of Fujian Province, No. 2003-1-19
文摘AIM： To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS： Fifty-four SD rats were randomly divided into ischemic preconditioning group （IP）, ischemia/ reperfusion group （IR） and sham operation group （SO）. The IP and IR groups were further divided into four sub-groups （n = 6）. Sham operation group （SO） served as the control group （n = 6）. A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. Alter 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinD1 mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration. RESULTS： Compared with IR group, IP group showed a significantly lower ALT level in 1h to 4h sub-groups （P 〈 0.05）. Proliferation index（PI） indicated by the S-phase and G2/M-phase ratio [（S＋G2/M）/（G0/G1＋S＋G2/M）] was significantly increased in IP group at 0 and 1 h （26.44 ± 7.60% vs 18.56 ± 6.40%,41.87 ± 7.27% vs 20.25 ± 6.70%, P 〈 0.05）. Meanwhile, cyclinD1 protein expression could be detected in IP group. But in IR group, cyclinD1 protein expression occurred 2 h alter reperfusion. The expression of cyclinD1 mRNA increased significantly in IP group at 0 and 1h （0.568 ± 0.112 vs 0.274 ± 0.069, 0.762 ± 0.164 vs 0.348 ± 0.093,P 〈 0.05）.CONCLUSION： Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.
文摘Objective： To study the relationship between expressions of α-, β-catenins and cyclin D1 and the occurrence, infiltration and metastasis of breast cancer. Methods： High sensitive S-P immunohistochemical method was used to detect the protein expressions of α-, β-catenins and cyclin D1 in the 60 cases of breast cancer tissues. Results： Abnormal immunoreactivities of α- and β-catenins were observed in 37 （61.7%） and 42 （70%） cases of breast cancer tissues, respectively. There were 28 cases （46.7%） who showed cyclin D1 overexpression. The abnormal expression rates of α- and β-catenins in infiltrating Iobular carcinoma （ILC） were significantly higher than those in infiltrating ductal carcinoma （IDC） （P 〈 0.05）, but they had no relations to the extent of differentiation and lymphatic metastasis of breast cancer （P 〉 0.05）. The overexpression rate of cyclin D1 was correlated with tumor stage and lymphatic metastasis of breast cancer （P 〈 0.05）, but not with histological type and the extent of differentiation （P 〉 0.05）. Cyclin D1 overexpression was observed in 57.1% （24/42） of these cases that showed abnormal staining of β-catenin, but only observed in 22.2% （4/18） of these cases with normal membranous staining of β-catenin. There was a significantly positive correlation between the abnormal expression of β-catenin and overexpression of cyclin D1 （r, = 0.321, P 〈 0.05）. Conclusion： The abnormal expression of β-catenin may play an important role in the genesis of breast cancer by triggering cyclin D1 overexpression in breast cancer. The abnormal expressions of α- and β-catenins are not a key factor in malignant cell metastasis in breast cancer, but may also involve in the progress.
基金Supported by the National Natural Science Foundation of China,No.30160096Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.0007037 and No.0342020
文摘AIM:To understand the role of P120ctn in E-cadherin-mediated cell-cell adhesion and signaling as well as inhepatoma cell biological function.METHODS:We stably overexpressed p120ctn isoform3A in BEL-7404 human hepatoma cells and studied theeffect of p120ctn on β-catenin and E-cadherin bindingas well as p120ctn and β-catenin subcellular localizationusing immunoprecipitation,Western blotting and confocalmicroscopy.We also investigated the inhibitory effectof p120ctn transfection on the expression of apoptoticprotein survivin survivin and cell cycle regulator cyclin D1in the cells.RERULTS:Western blotting indicated that p120ctnexpression increased after cells were transfected withp120ctn isoform 3A.The protein was located mainlyat membrane under immunofluorescent microscope.β-catenin nuclear expression was reduced afteroverexpression of p120ctn isoform 3A.The p120ctn-E-cadherin binding increased after transfection of p120ctnisoform 3A.Furthermore,overexpression of p120ctndown regulated the expression of apoptotic protein sur-vivin and cell cycle regulator cyclin D1.These effects ledto reduction of cell proliferation.CONCLUSION:Our results indicate that p120ctnplays an important role in regulating the formation ofE-cadherin and-catenin complex,cell apoptosis,cellcycle and cancer cell biological function.
文摘Objective: To study cyclinD1/bcl-1 and p27/kip1 expression in gliomas and their correlation with pathological grade and prognosis. Methods: Immunohistochemical technique was used to detect the cyclinD1/bcl-1 and p27/kip1 expression in 48 human brain glioma tissues of different malignant grades, and 12 normal non-neoplastic tissues collected from internal decompression. The data were analyzed quantitatively by the image system and also correlated retrospectively with the patients' clinical characteristics. Results: The immunohistochemical reaction for cyclinD1/bcl-1 and p27/kip1 was confined to the nuclei. The abnormal positive expression rates of both cyclinD1/bcl-1 and p27/kip1 in gliomas were found higher than that in non-neoplastic tissues(P<0.05). The number and staining intensity of cyclinD1/bcl-1 positive nuclei increased with malignant grades (P<0.05). On the contrary, the positive nuclei of p27/kip1 expression decreased in number and staining intensity with malignant grades(P<0.05). Higher expression of cyclinD1/bcl-1 or/and lower expression of p27/kip1 were associated with poor prognosis(P<0.05). Conclusion: The abnormal expression of both cyclinD1/bcl-1 and p27/kip1 might be closely related to the occurrence and development of gliomas and they might have synergistic effect. These data suggest that both cyclinD1/bcl-1 expression and p27/kip1 expression can act as an independent prognostic factor.
