进展期胃癌NF-κB及Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结癌细胞再表达的关系及其临床意义
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摘要
目的:进展期胃癌NF-κB及Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结癌细胞再表达的关系及其临床意义,探讨NF-κB、Rb蛋白与E-cadherin/catenin复合物对胃癌转移机制和对患者预后的影响。寻求在分子水平对胃癌早期诊断和治疗更新、更有效的方法。
方法:用采用免疫组化过氧化物酶标记链霉卵白素法(SP)分别检测了NF-κB、Rb蛋白在肿瘤原发灶与E-cadherin/catenin复合物在86例进展期胃癌原发灶及其相应淋巴结内癌细胞的表达情况,并结合肿瘤的大小、浸润深度、分化程度、组织学类型、淋巴结转移和患者的预后等临床病理因素进行综合分析。
结果:NF-κB、Rb蛋白与E-cadherin/catenin复合物免疫阳性产物均为棕黄色,NF-κB、Rb染色定位于细胞浆或细胞核,E-cadherin、α-、β-及γ-catenin染色定位于细胞膜。NF-κB蛋白在86例进展期胃癌组织中表达阳性率达81.40% (70/86),Rb蛋白在86例进展期胃癌组织中表达阳性率达65.12% (56/86),E-cadherin/catenin复合物在肿瘤原发灶只有1例正常表达,85例不正常表达,异常表达率为98.84%,该复合物在转移淋巴结内癌细胞中再表达阳性率为63.95%(55/86)。NF-κB的表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)密切相关,在管状腺癌中阳性表达率为85.96% (49/57),在粘液腺癌中阳性表达率为61.90% (13/21),差异显著(P < 0.05);NF-κB的表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为91.43% (32/35),在低分化胃癌中的表达阳性率为74.51% (38/51),差异显著(P < 0.05);NF-κB的表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为83.08% (54/65),在直径小于5cm从肿瘤中阳性表达率为76.19% (16/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为82.05% (64/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为75.00% (6/8),差异无显著性(P > 0.05)。Rb蛋白的表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为85.71% (30/35),在低分化胃癌中的表达阳性率为50.98% (26/51),差异显著(P < 0.05);Rb蛋白的表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)无关,在管状腺癌中阳性表达率为70.18% (40/57),在粘液腺癌中阳性表达率为71.43% (15/21),差异无显著性(P > 0.05);Rb蛋白的表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为60.00% (39/65),在直径小于5cm从肿瘤中阳性表达率为80.95% (17/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为74.36% (50/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为75.00% (6/8),差异无显著性(P > 0.05)。E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为77.14% (27/35),在低分化胃癌中的表达阳性率为54.90% (28/51),差异显著(P < 0.05);E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)无关,在管状腺癌中阳性表达率为73.68% (42/57),在粘液腺癌中阳性表达率为52.38% (11/21),差异无显著性(P > 0.05);E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为64.62% (42/65),在直径小于5cm从肿瘤中阳性表达率为61.90% (13/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为74.36% (50/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为62.50% (5/8),差异无显著性(P > 0.05)(见表2)。Kaplan-Meier曲线显示NF-κB、Rb蛋白的表达与患者的预后无关(P > 0.05)(见图1、2);E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达情况与患者的预后密切相关(P < 0.05)(见图3)。Wilcoxon’s log-rank test进行组间差别检验显示各组间差别无显著性(P > 0.05)(见表3)。Cox’s proportional-hazard多变量分析显示E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达可以作为一个独立的预后因素(P < 0.05)(见表4)。Spearman秩相关分析显示NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达均无显著相关性(见表5、6、7)。
结论:NF-κB、Rb蛋白与E-cadherin/catenin复合物可能与胃癌的发生、发展和转移密切相关;胃癌中存在NF-κB、Rb蛋白的高表达,转移淋巴结癌细胞中存在E-cadherin/catenin复合物的高再表达;E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达情况与患者的预后密切相关,可以作为一个独立的预后因素,NF-κB、Rb蛋白的表达与预后无关;NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达三者间无显著相关性。临床可以通过检测NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达提高早期诊断和早期治疗的敏感性并改善预后。
Objective: The aim of this study was to study the expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes from advanced gastric carcinoma,and to evaluate its clinical significance,to investigate the unite factor effect of NF-κB, Rb and E-cadherin/catenin complex for metastatic mechanism of gastric carcinoma and prognosis. Therefore , to look for a kind of more sensitive and reliable method for early period diagnosis and early period remedy in a molecule level of gastric carcinoma.
Methods: S-P immunohistochemical technique was used to examine the expression of NF-κB, Rb in primary advanced gastric carcinoma and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes from 86 advanced gastric carcinoma. The level of the expression was analyzed combined with clinicopathological features of the size of the tumor, infiltration depth, pathological differentiation, tumor pathological stages, lymph node metastasis and prognosis.
Results: The color of the immune positive products of NF-κB,Rb was buffy and located in cytoplasm or nucleus and E-cadherin/catenin complex was buffy and located in plasmalemma. The rate of positive expression of NF-κB was 81.40% (70/86) in primary advanced gastric carcinoma. The rate of positive expression of Rb was 65.12% (56/86) in primary advanced gastric carcinoma. The rate of positive re-expression of E-cadherin/catenin complex was 63.95% (55/86) in cancerous cells of metastatic lymph nodes from advanced gastric carcinoma. The expression of NF-κB was lower in mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 61.90% (13/21) and 85.96% (49/57) respectively (P < 0.05). The expression of NF-κB was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 74.51% (38/51) and 91.43% (32/35) respectively (P < 0.05). The expression of NF-κB was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 83.08% (54/65) and 76.19% (16/21) respectively (P > 0.05). The expression of NF-κB was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 82.05% (64/78) and 75.00% (6/8) respectively (P > 0.05). The expression of Rb was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 74.51% (38/51) and 85.71% (30/35) respectively (P < 0.05). The expression of Rb was not remarkable difference in the mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 70.18% (40/57) and 71.43% (15/21) respectively (P > 0.05). The expression of Rb was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 60.00% (39/65) and 80.95% (17/21) respectively (P > 0.05). The expression of Rb was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 74.36% (50/78) and 75.00% (6/8) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 54.90% (28/51) and 77.14% (27/35) respectively (P < 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 52.38% (11/21) and 73.68% (42/57) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 64.62% (42/65) and 61.90% (13/21) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 74.36% (50/78) and 62.50% (5/8) respectively. There is no remarkable difference between the groups by Wilcoxon’s log-rank test. And the Cox’s proportional-hazard show that the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was a independent factor of prognosis. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not significant correlated among each (P > 0.05).
Conclusion: NF-κB, Rb and E-cadherin/catenin complex may be closely correlated to the occurrence, the advancement and the metastasis of gastric carcinoma. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was increased from advanced gastric carcinoma. The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was closely correlated and could be a independent factor of prognosis. The expression of NF-κB, Rb was not correlated to the prognosis. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not significant correlated among each. Therefore, NF-κB, Rb and E-cadherin/catenin complex could be checked to enhance the sensitivity of diagnosis and remedy early period and to improve the prognosis.
方法:用采用免疫组化过氧化物酶标记链霉卵白素法(SP)分别检测了NF-κB、Rb蛋白在肿瘤原发灶与E-cadherin/catenin复合物在86例进展期胃癌原发灶及其相应淋巴结内癌细胞的表达情况,并结合肿瘤的大小、浸润深度、分化程度、组织学类型、淋巴结转移和患者的预后等临床病理因素进行综合分析。
结果:NF-κB、Rb蛋白与E-cadherin/catenin复合物免疫阳性产物均为棕黄色,NF-κB、Rb染色定位于细胞浆或细胞核,E-cadherin、α-、β-及γ-catenin染色定位于细胞膜。NF-κB蛋白在86例进展期胃癌组织中表达阳性率达81.40% (70/86),Rb蛋白在86例进展期胃癌组织中表达阳性率达65.12% (56/86),E-cadherin/catenin复合物在肿瘤原发灶只有1例正常表达,85例不正常表达,异常表达率为98.84%,该复合物在转移淋巴结内癌细胞中再表达阳性率为63.95%(55/86)。NF-κB的表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)密切相关,在管状腺癌中阳性表达率为85.96% (49/57),在粘液腺癌中阳性表达率为61.90% (13/21),差异显著(P < 0.05);NF-κB的表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为91.43% (32/35),在低分化胃癌中的表达阳性率为74.51% (38/51),差异显著(P < 0.05);NF-κB的表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为83.08% (54/65),在直径小于5cm从肿瘤中阳性表达率为76.19% (16/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为82.05% (64/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为75.00% (6/8),差异无显著性(P > 0.05)。Rb蛋白的表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为85.71% (30/35),在低分化胃癌中的表达阳性率为50.98% (26/51),差异显著(P < 0.05);Rb蛋白的表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)无关,在管状腺癌中阳性表达率为70.18% (40/57),在粘液腺癌中阳性表达率为71.43% (15/21),差异无显著性(P > 0.05);Rb蛋白的表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为60.00% (39/65),在直径小于5cm从肿瘤中阳性表达率为80.95% (17/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为74.36% (50/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为75.00% (6/8),差异无显著性(P > 0.05)。E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤细胞的分化程度密切相关,在中高分化胃癌中的表达阳性率为77.14% (27/35),在低分化胃癌中的表达阳性率为54.90% (28/51),差异显著(P < 0.05);E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤细胞的病理类型(印戒细胞癌、未分化癌、磷癌及腺磷癌因样本含量过小,故未予统计)无关,在管状腺癌中阳性表达率为73.68% (42/57),在粘液腺癌中阳性表达率为52.38% (11/21),差异无显著性(P > 0.05);E-cadherin/catenin复合物在转移淋巴结癌细胞中的再表达与肿瘤大小及肿瘤浸润深度无关,在直径大于5cm的肿瘤中阳性表达率为64.62% (42/65),在直径小于5cm从肿瘤中阳性表达率为61.90% (13/21),差异无显著性(P > 0.05);在浸润深度侵及浆膜层的肿瘤中阳性表达率为74.36% (50/78),在浸润深度未侵及浆膜层的肿瘤中阳性表达率为62.50% (5/8),差异无显著性(P > 0.05)(见表2)。Kaplan-Meier曲线显示NF-κB、Rb蛋白的表达与患者的预后无关(P > 0.05)(见图1、2);E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达情况与患者的预后密切相关(P < 0.05)(见图3)。Wilcoxon’s log-rank test进行组间差别检验显示各组间差别无显著性(P > 0.05)(见表3)。Cox’s proportional-hazard多变量分析显示E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达可以作为一个独立的预后因素(P < 0.05)(见表4)。Spearman秩相关分析显示NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达均无显著相关性(见表5、6、7)。
结论:NF-κB、Rb蛋白与E-cadherin/catenin复合物可能与胃癌的发生、发展和转移密切相关;胃癌中存在NF-κB、Rb蛋白的高表达,转移淋巴结癌细胞中存在E-cadherin/catenin复合物的高再表达;E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达情况与患者的预后密切相关,可以作为一个独立的预后因素,NF-κB、Rb蛋白的表达与预后无关;NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达三者间无显著相关性。临床可以通过检测NF-κB、Rb蛋白的表达与E-cadherin/catenin复合物在转移淋巴结内癌细胞中再表达提高早期诊断和早期治疗的敏感性并改善预后。
Objective: The aim of this study was to study the expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes from advanced gastric carcinoma,and to evaluate its clinical significance,to investigate the unite factor effect of NF-κB, Rb and E-cadherin/catenin complex for metastatic mechanism of gastric carcinoma and prognosis. Therefore , to look for a kind of more sensitive and reliable method for early period diagnosis and early period remedy in a molecule level of gastric carcinoma.
Methods: S-P immunohistochemical technique was used to examine the expression of NF-κB, Rb in primary advanced gastric carcinoma and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes from 86 advanced gastric carcinoma. The level of the expression was analyzed combined with clinicopathological features of the size of the tumor, infiltration depth, pathological differentiation, tumor pathological stages, lymph node metastasis and prognosis.
Results: The color of the immune positive products of NF-κB,Rb was buffy and located in cytoplasm or nucleus and E-cadherin/catenin complex was buffy and located in plasmalemma. The rate of positive expression of NF-κB was 81.40% (70/86) in primary advanced gastric carcinoma. The rate of positive expression of Rb was 65.12% (56/86) in primary advanced gastric carcinoma. The rate of positive re-expression of E-cadherin/catenin complex was 63.95% (55/86) in cancerous cells of metastatic lymph nodes from advanced gastric carcinoma. The expression of NF-κB was lower in mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 61.90% (13/21) and 85.96% (49/57) respectively (P < 0.05). The expression of NF-κB was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 74.51% (38/51) and 91.43% (32/35) respectively (P < 0.05). The expression of NF-κB was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 83.08% (54/65) and 76.19% (16/21) respectively (P > 0.05). The expression of NF-κB was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 82.05% (64/78) and 75.00% (6/8) respectively (P > 0.05). The expression of Rb was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 74.51% (38/51) and 85.71% (30/35) respectively (P < 0.05). The expression of Rb was not remarkable difference in the mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 70.18% (40/57) and 71.43% (15/21) respectively (P > 0.05). The expression of Rb was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 60.00% (39/65) and 80.95% (17/21) respectively (P > 0.05). The expression of Rb was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 74.36% (50/78) and 75.00% (6/8) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was lower in poor differentiation degree than those in high and moderate differentiation degree and the rate of positive expression was 54.90% (28/51) and 77.14% (27/35) respectively (P < 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the mucinous adenocarcinoma than those in adencarcinoma and the rate of positive expression was 52.38% (11/21) and 73.68% (42/57) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the diameter in the primary advanced gastric carcinoma and the rate of positive expression was 64.62% (42/65) and 61.90% (13/21) respectively (P > 0.05). The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not remarkable difference in the infiltrated range limited to muscle stratum than serosa stratum and the rate of positive expression was 74.36% (50/78) and 62.50% (5/8) respectively. There is no remarkable difference between the groups by Wilcoxon’s log-rank test. And the Cox’s proportional-hazard show that the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was a independent factor of prognosis. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not significant correlated among each (P > 0.05).
Conclusion: NF-κB, Rb and E-cadherin/catenin complex may be closely correlated to the occurrence, the advancement and the metastasis of gastric carcinoma. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was increased from advanced gastric carcinoma. The re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was closely correlated and could be a independent factor of prognosis. The expression of NF-κB, Rb was not correlated to the prognosis. The expression of NF-κB, Rb and the re-expression of E-cadherin/catenin complex in cancerous cells of metastatic lymph nodes was not significant correlated among each. Therefore, NF-κB, Rb and E-cadherin/catenin complex could be checked to enhance the sensitivity of diagnosis and remedy early period and to improve the prognosis.
引文
1 Andrews NA, Jones AS, Heliwell TR, et al. Expression of the E-cadherin-catenin cell adhesion complex in primary squamous cell carcinoma of the head and neck and their nodal metastases. Br J Cancer, 1997, 75(10):1474-1480.
2 Grumont RJ , Rourke IJ , Strasser A , et al .B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-KappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogfenactivated cell [J] . J Exp Med, 1998, 187(5) : 663-674 .
3 de Martin R, Schmid JA, Hofer Warbinek R, et al. The NF-KappaB/Rcl family of transcription factors in oncogenic transformation and apoptosis[J]. Mutat Res, 1999, 4379 (3):231-43.
4 於亮亮, 于皆平, 冉宗学. 核因子与大肠肿瘤细胞凋亡及增生的关系[J]. 世界华人消化杂志,2002,1(3):309-312 .
5 王维, 罗和生, 余保平. 胃癌及癌前病变中核因子-kappaB 和端粒酶逆转录酶的表达与意义[J]. 中国癌症杂志, 2002, 12(4): 289-292.
6 La Rosa FA, Pierce JW,Sonenshein GE, et al. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors [J]. Mol cell biol, 1994, 14(2):1039-1044.
7 Ryan KM, Ernst MK, Rice NR, et al. Role of NF-kappa B in p53-mediated programmed cell death [J]. Nature, 2000, 404(6780):892-7.
8 Jo H, Zhang R, Zhang H, Mckinsey TA, et al. NF-kappa B is required for H-ras oncogene inducedab normal cell proliferation and tumorigenesis [J]. Oncogene, 2000, 19(7):841-9
9 Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis [J]. Cell, 1994, 79(2):185-8
10 Sasaki N, Morisaki T, Hashizume K, et al. Nuclear factor-kappa B p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue [J]. Clin Cancer Res, 2001, 7(12):4136-42
11 Mittnach S, Weinberg RA. G1/S phosphorylation of the retinoblastomas protein is associated with an altered affinity for the nuclear compartment [J]. Cell 1991; 65(3) : 381-93
12 Robbins PD, Horowitz JM, Mulligan RC, et al. Negative regulation of human C-fos expression by retinoblastomas gene product [J]. Nature 1990 ; 346(6285) : 668-71
13 Hinck L, Nelson WJ, Papkoff J. Wnt-1 modulates cell-celladhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin[J]. J Cell Biol, 1994, 124(5): 729-41.
14 Naqar B, Overduin M, Ikura M, et al. Structural basis of calcium-induced E-cadherin rigidification and dimerization [J]. Nature, 1996, 380(6572): 360-4
15 Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator [J]. Science, 1991, 251(5000): 1451-5
16 Brachenbury Y. Molecular mechanisms of cell adhesion in normal and transformed cells[J]. Cancer Metastasis Rev, 1995, 4(1): 41-58
17 Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival[J]. Gastroecterology, 1997, 112(1):46-54.
18 Bukholm IK, Nesland JM, Borresen Dale Al,Re-expression of E-cadherin, α- and β-catenin, but not of γ-catenin, in metastatic tissue from breast cancer patients [J] . J Pathol , 2000, 190(1) : 15-19
19 Brabletz T, Jung A, Hermann K, et al. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front [J]. Pathol Res Pract. 1998, 194(10):701-4
20 刘津,池口正英,闫庆辉,等. 钙粘蛋白-链蛋白复合体在进展期胃癌转移淋巴结的再表达及其临床意义. 中华实验外科杂志,2004,21:535-537
21 He TC, Sparks AB, Raqo C, et al. Identification of c-myc as a target of the APC pathway [J]. Science, 1998, 281(5328):1509-12
22 FitzGerald MJ, Webber EM, Donovan JR, et al. Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration [J]. Cell Growth Differ, 1995, 6(4):417-27
23 Guttridge DC, Albanese C, Reuther JY, et al. NF-κb controls cell growth and differentiation through transcriptional regulation of Cyclin D1 [J]. Mol Cell Biol, 1999, 19(8): 5785-99
1 Nollet F, Berx G, van Roy F. The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer [J]. Cell Biol Res Commun, 1999, 2(2): 77-83
2 Nagar B, Overduin M, Ikura M, et al. Structural basis of calcium-induced E-cadherin rigidification and dimerization [J]. Nature, 1996, 380(6572): 360-4
3 Takeichi M. Cadherin cell cadherin receptors as a morphogenetic regulator[J]. Science, 1991, 251(5000): 1451-5
4 Brachenbury Y. Molecular mechanisms of cell adhesion in normal and transformed cells[J]. Cancer Metastasis Rev, 1995, 4(1): 41-58
5 Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival[J].Gastroecterology, 1997, 112(1): 46-54
6 Bukholm IK, Nesland JM, Borresen Dale Al,Re-expression of E-cadherin, α- and β-catenin, but not of γ-catenin, in metastatic tissue from breast cancer patients [J] . J Pathol , 2000, 190(1): 15-19
7 Brabletz T, Jung A, Hermann K, et al. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front [J]. Pathol Res Pract. 1998,194(10): 701-4
8 Rubinfeld B, Suzan B, Albert I, et al. The APC protein and E-cadherin form similar but independent complexes with α- ,β- and plakoglobin [J] . J Biol Chem, 1995, 270(10): 5549-55
9 Shibamoto S, Hayakawa M, Takeuchi K, et al. Tyrosine phosphorylation of β-catenin and plakoglobin enhanced by heprocyte growth factor and epidermal growth factor in human carcinoma cells [J] .Cell Adhes Commun, 1994, 1(4): 295-305
10 Ochiai A, Aakimoto S, Kana Y, et al, C-erbB-2 gene product associates with catenins in human cancer cells [J] .Biochem Biophys Res Commun, 1995, 208(3): 73-8
11 Hazan RB, Kang L, Roe S, et sl. Vinculin is associated with the E-cadherin adhesion complex [J]. J Biol chem, 1997, 272(51): 32448-53
12 He TC , Sparks AB , Raqo C , et al. Identification of c-myc as a target of the APC pathway [J]. Science, 1998,281(5328): 1509-12
13 戴冬秋, 陈峻青, 徐惠绵, 等. E-钙黏附素及 α-链接素的表达与胃癌生物学行为及淋巴结转移规律的关系. 中华肿瘤杂志, 2001, 23: 35-38
14 Gabbert HE, Mueller W, Schneiders A, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas [J]. Int J Cancer, 1996, 69(3): 184-9
15 Joo YE, Rew JS, Kim HS, et al. Changes in the E-cadherin-catenin complex expression in early and advanced gastric cancers [J], Digestion, 2001, 64(2): 111-9
16 刘津,池口正英,闫庆辉,等. 钙粘蛋白-链蛋白复合体在进展期胃癌转移淋巴结的再表达及其临床意义. 中华实验外科杂志,2004,21: 535-537
17 许 斌, 王新娟. Rb 在细胞调控中的作用.国外医学分子生物学分册 1995; 17 (5): 211
18 Peter M, Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle [J]. Cell, 1994, 79(2): 181-4
19 Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types [J]. Science 1994, 264 (5157): 436-40
20 Gunther T, Schheider-Stock R, Pross M, et al. Alterations of the p16/MTS1- tumor suppressor gene in gastric cancer [J]. Pathol Res Pract, 1998, 194 (12): 809-13
21 Mittnach S, Weinberg RA. G1/S phosphorylation of the retinoblastomas protein is associated with an altered affinityfor the nuclear compartment. Cell 1991; 65(3): 381-93
22 Robbins PD, Horowitz JM, Mulligan RC, et al. Negative regulation of human C-fos expression by retinoblastomas gene product [J]. Nature 1990 ; 346(6285): 668-71
23 Grumont RJ , Rourke IJ , Strasser A , et al .B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-KappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogfenactivated cell [J] . J Exp Med , 1998 , 187(5): 663-74
24 Ninomiya I, Yonemura Y, Matsumoto H, et al. Expression of c-myc gene product in gastric carcinoma[J]. Oncology, 1991, 48(2): 149-53
25 Hale AJ, Smith CA, Sutherland LC, et al. Molecular regulation of cell death [J]. Eur J Biochem, 1996, 236(1): 1-26
26 de Martin R , Schmid JA , Hofer Warbinek R, et al .The NF-KappaB/Rcl family of transcription factors in oncogenic transformation and apoptosis[J] . Mutat Res ,1999 , 4379(3): 231-43
27 於亮亮,于皆平,冉宗学.核因子与大肠肿瘤细胞凋亡及增生的关系[J].世界华人消化杂志,2002,10(3): 309-312
28 FitzGerald MJ, Webber EM, Donovan JR, et al. Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration [J]. Cell Growth Differ, 1995, 6(4): 417-27
29 Guttridge DC, Albanese C, Reuther JY, et al. NF-κb controls cell growth and differentiation through transcriptional regulation of Cyclin D1 [J]. Mol Cell Biol, 1999,19(8): 5785-99
30 王维,罗和生,余保平.胃癌及癌前病变中核因子-kappaB 和端 粒 酶 逆 转 录 酶 的 表 达 与 意 义 [J]. 中 国 癌 症 杂志,2002,12(4): 289-292
31 La Rosa FA, Pierce JW ,Sonenshein GE, et al. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors [J]. Mol cell biol, 1994, 14(2): 1039-44
32 Ryan KM, Ernst MK, Rice NR, et al. Role of NF-kappa B in p53-mediated programmed cell death. Nature, 2000, 404(6780):892-7
33 Jo H, Zhang R, Zhang H, et al. NF-kappa B is required for H-ras oncogene inducedab normal cell proliferation and tumorigenesis. Oncogene, 2000,19(7): 841-9
34 Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell, 1994,79(2): 185-8
35 Sasaki N, Morisaki T, Hashizume K, et al. Nuclear factor-kappa B p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue [J]. Clin Cancer Res, 2001, 7(12): 4136-42
2 Grumont RJ , Rourke IJ , Strasser A , et al .B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-KappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogfenactivated cell [J] . J Exp Med, 1998, 187(5) : 663-674 .
3 de Martin R, Schmid JA, Hofer Warbinek R, et al. The NF-KappaB/Rcl family of transcription factors in oncogenic transformation and apoptosis[J]. Mutat Res, 1999, 4379 (3):231-43.
4 於亮亮, 于皆平, 冉宗学. 核因子与大肠肿瘤细胞凋亡及增生的关系[J]. 世界华人消化杂志,2002,1(3):309-312 .
5 王维, 罗和生, 余保平. 胃癌及癌前病变中核因子-kappaB 和端粒酶逆转录酶的表达与意义[J]. 中国癌症杂志, 2002, 12(4): 289-292.
6 La Rosa FA, Pierce JW,Sonenshein GE, et al. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors [J]. Mol cell biol, 1994, 14(2):1039-1044.
7 Ryan KM, Ernst MK, Rice NR, et al. Role of NF-kappa B in p53-mediated programmed cell death [J]. Nature, 2000, 404(6780):892-7.
8 Jo H, Zhang R, Zhang H, Mckinsey TA, et al. NF-kappa B is required for H-ras oncogene inducedab normal cell proliferation and tumorigenesis [J]. Oncogene, 2000, 19(7):841-9
9 Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis [J]. Cell, 1994, 79(2):185-8
10 Sasaki N, Morisaki T, Hashizume K, et al. Nuclear factor-kappa B p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue [J]. Clin Cancer Res, 2001, 7(12):4136-42
11 Mittnach S, Weinberg RA. G1/S phosphorylation of the retinoblastomas protein is associated with an altered affinity for the nuclear compartment [J]. Cell 1991; 65(3) : 381-93
12 Robbins PD, Horowitz JM, Mulligan RC, et al. Negative regulation of human C-fos expression by retinoblastomas gene product [J]. Nature 1990 ; 346(6285) : 668-71
13 Hinck L, Nelson WJ, Papkoff J. Wnt-1 modulates cell-celladhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin[J]. J Cell Biol, 1994, 124(5): 729-41.
14 Naqar B, Overduin M, Ikura M, et al. Structural basis of calcium-induced E-cadherin rigidification and dimerization [J]. Nature, 1996, 380(6572): 360-4
15 Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator [J]. Science, 1991, 251(5000): 1451-5
16 Brachenbury Y. Molecular mechanisms of cell adhesion in normal and transformed cells[J]. Cancer Metastasis Rev, 1995, 4(1): 41-58
17 Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival[J]. Gastroecterology, 1997, 112(1):46-54.
18 Bukholm IK, Nesland JM, Borresen Dale Al,Re-expression of E-cadherin, α- and β-catenin, but not of γ-catenin, in metastatic tissue from breast cancer patients [J] . J Pathol , 2000, 190(1) : 15-19
19 Brabletz T, Jung A, Hermann K, et al. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front [J]. Pathol Res Pract. 1998, 194(10):701-4
20 刘津,池口正英,闫庆辉,等. 钙粘蛋白-链蛋白复合体在进展期胃癌转移淋巴结的再表达及其临床意义. 中华实验外科杂志,2004,21:535-537
21 He TC, Sparks AB, Raqo C, et al. Identification of c-myc as a target of the APC pathway [J]. Science, 1998, 281(5328):1509-12
22 FitzGerald MJ, Webber EM, Donovan JR, et al. Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration [J]. Cell Growth Differ, 1995, 6(4):417-27
23 Guttridge DC, Albanese C, Reuther JY, et al. NF-κb controls cell growth and differentiation through transcriptional regulation of Cyclin D1 [J]. Mol Cell Biol, 1999, 19(8): 5785-99
1 Nollet F, Berx G, van Roy F. The role of the E-cadherin/catenin adhesion complex in the development and progression of cancer [J]. Cell Biol Res Commun, 1999, 2(2): 77-83
2 Nagar B, Overduin M, Ikura M, et al. Structural basis of calcium-induced E-cadherin rigidification and dimerization [J]. Nature, 1996, 380(6572): 360-4
3 Takeichi M. Cadherin cell cadherin receptors as a morphogenetic regulator[J]. Science, 1991, 251(5000): 1451-5
4 Brachenbury Y. Molecular mechanisms of cell adhesion in normal and transformed cells[J]. Cancer Metastasis Rev, 1995, 4(1): 41-58
5 Jawhari A, Jordan S, Poole S, et al. Abnormal immunoreactivity of the E-cadherin-catenin complex in gastric carcinoma: relationship with patient survival[J].Gastroecterology, 1997, 112(1): 46-54
6 Bukholm IK, Nesland JM, Borresen Dale Al,Re-expression of E-cadherin, α- and β-catenin, but not of γ-catenin, in metastatic tissue from breast cancer patients [J] . J Pathol , 2000, 190(1): 15-19
7 Brabletz T, Jung A, Hermann K, et al. Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front [J]. Pathol Res Pract. 1998,194(10): 701-4
8 Rubinfeld B, Suzan B, Albert I, et al. The APC protein and E-cadherin form similar but independent complexes with α- ,β- and plakoglobin [J] . J Biol Chem, 1995, 270(10): 5549-55
9 Shibamoto S, Hayakawa M, Takeuchi K, et al. Tyrosine phosphorylation of β-catenin and plakoglobin enhanced by heprocyte growth factor and epidermal growth factor in human carcinoma cells [J] .Cell Adhes Commun, 1994, 1(4): 295-305
10 Ochiai A, Aakimoto S, Kana Y, et al, C-erbB-2 gene product associates with catenins in human cancer cells [J] .Biochem Biophys Res Commun, 1995, 208(3): 73-8
11 Hazan RB, Kang L, Roe S, et sl. Vinculin is associated with the E-cadherin adhesion complex [J]. J Biol chem, 1997, 272(51): 32448-53
12 He TC , Sparks AB , Raqo C , et al. Identification of c-myc as a target of the APC pathway [J]. Science, 1998,281(5328): 1509-12
13 戴冬秋, 陈峻青, 徐惠绵, 等. E-钙黏附素及 α-链接素的表达与胃癌生物学行为及淋巴结转移规律的关系. 中华肿瘤杂志, 2001, 23: 35-38
14 Gabbert HE, Mueller W, Schneiders A, et al. Prognostic value of E-cadherin expression in 413 gastric carcinomas [J]. Int J Cancer, 1996, 69(3): 184-9
15 Joo YE, Rew JS, Kim HS, et al. Changes in the E-cadherin-catenin complex expression in early and advanced gastric cancers [J], Digestion, 2001, 64(2): 111-9
16 刘津,池口正英,闫庆辉,等. 钙粘蛋白-链蛋白复合体在进展期胃癌转移淋巴结的再表达及其临床意义. 中华实验外科杂志,2004,21: 535-537
17 许 斌, 王新娟. Rb 在细胞调控中的作用.国外医学分子生物学分册 1995; 17 (5): 211
18 Peter M, Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle [J]. Cell, 1994, 79(2): 181-4
19 Kamb A, Gruis NA, Weaver-Feldhaus J, et al. A cell cycle regulator potentially involved in genesis of many tumor types [J]. Science 1994, 264 (5157): 436-40
20 Gunther T, Schheider-Stock R, Pross M, et al. Alterations of the p16/MTS1- tumor suppressor gene in gastric cancer [J]. Pathol Res Pract, 1998, 194 (12): 809-13
21 Mittnach S, Weinberg RA. G1/S phosphorylation of the retinoblastomas protein is associated with an altered affinityfor the nuclear compartment. Cell 1991; 65(3): 381-93
22 Robbins PD, Horowitz JM, Mulligan RC, et al. Negative regulation of human C-fos expression by retinoblastomas gene product [J]. Nature 1990 ; 346(6285): 668-71
23 Grumont RJ , Rourke IJ , Strasser A , et al .B lymphocytes differentially use the Rel and nuclear factor kappaB1 (NF-KappaB1) transcription factors to regulate cell cycle progression and apoptosis in quiescent and mitogfenactivated cell [J] . J Exp Med , 1998 , 187(5): 663-74
24 Ninomiya I, Yonemura Y, Matsumoto H, et al. Expression of c-myc gene product in gastric carcinoma[J]. Oncology, 1991, 48(2): 149-53
25 Hale AJ, Smith CA, Sutherland LC, et al. Molecular regulation of cell death [J]. Eur J Biochem, 1996, 236(1): 1-26
26 de Martin R , Schmid JA , Hofer Warbinek R, et al .The NF-KappaB/Rcl family of transcription factors in oncogenic transformation and apoptosis[J] . Mutat Res ,1999 , 4379(3): 231-43
27 於亮亮,于皆平,冉宗学.核因子与大肠肿瘤细胞凋亡及增生的关系[J].世界华人消化杂志,2002,10(3): 309-312
28 FitzGerald MJ, Webber EM, Donovan JR, et al. Rapid DNA binding by nuclear factor kappa B in hepatocytes at the start of liver regeneration [J]. Cell Growth Differ, 1995, 6(4): 417-27
29 Guttridge DC, Albanese C, Reuther JY, et al. NF-κb controls cell growth and differentiation through transcriptional regulation of Cyclin D1 [J]. Mol Cell Biol, 1999,19(8): 5785-99
30 王维,罗和生,余保平.胃癌及癌前病变中核因子-kappaB 和端 粒 酶 逆 转 录 酶 的 表 达 与 意 义 [J]. 中 国 癌 症 杂志,2002,12(4): 289-292
31 La Rosa FA, Pierce JW ,Sonenshein GE, et al. Differential regulation of the c-myc oncogene promoter by the NF-kappa B rel family of transcription factors [J]. Mol cell biol, 1994, 14(2): 1039-44
32 Ryan KM, Ernst MK, Rice NR, et al. Role of NF-kappa B in p53-mediated programmed cell death. Nature, 2000, 404(6780):892-7
33 Jo H, Zhang R, Zhang H, et al. NF-kappa B is required for H-ras oncogene inducedab normal cell proliferation and tumorigenesis. Oncogene, 2000,19(7): 841-9
34 Fidler IJ, Ellis LM. The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell, 1994,79(2): 185-8
35 Sasaki N, Morisaki T, Hashizume K, et al. Nuclear factor-kappa B p65 (RelA) transcription factor is constitutively activated in human gastric carcinoma tissue [J]. Clin Cancer Res, 2001, 7(12): 4136-42