整合素β3,p38MAPK及MMP-2在乳腺癌中存在功能性的联系  

Integrin β3,p38 MAPK and MMP-2 are functionally linked in breast cancer

作　　者：王睿[1,2] 李照青[3] 宋敏[1,2] 李柏林[4] 温媛媛[1,2] 韩艳春[1,2] 赵艳[1,2] 王恩华[1,2] 

机构地区：[1]中国医科大学附属第一临床学院病理科暨基础医学院病理学教研室 [2]中国医科大学基础医学院病理生理学教研室 [3]北京人民医院,北京100044 [4]中国医科大学基础医学院化学教研室,辽宁沈阳110001

出　　处：《解剖科学进展》2011年第2期108-112,共5页Progress of Anatomical Sciences

基　　金：辽宁省教育厅基金资助项目(No.2008739);高等学校博士学科点专项科研基金联合资助课题(No.200801590017)

摘　　要：目的研究整合素β3与配体Tenascin-c(TN-c)在乳腺癌组织中的表达,探讨其是否通过p38丝裂原活化蛋白激酶(p38mitogen-activated protein kinase,p38MAPK)激活基质金属蛋白酶-2(MMP-2)。方法本研究应用免疫组化SP方法检测了80例乳腺浸润性导管癌中整合素β3及TN-c的表达,同时在培养的乳腺癌MDA-MB-231细胞系中分别阻断整合素β3和p38MAPK,应用Western Blot的方法,检测p-p38和MMP-2的表达情况。结果整合素β3和TN-c在乳腺浸润性导管癌组织中高表达,整合素β3与TN-c的表达之间存在相关性,并与乳腺癌的TNM分期及淋巴结转移相关。应用整合素β3的抗体抑制表达后,可以降低乳腺癌细胞系MDA-MB-231中p-p38以及MMP-2的表达量;用p38的特异性抑制剂SB203580进行阻断,可以降低MMP-2的表达量。结论乳腺浸润性导管癌中存在整合素β3和TN-c的高表达且它们的表达存在相关性,抑制整合素β3可以通过p38MAPK信号分子,抑制MMP-2的表达。Objective To determine the combined expression of integrin β3 and tenascin-c（TN-c） in human breast cancer and explore if integrin β3 activates matrix metalloproteinase-2（MMP-2） through p38 mitogen-activated protein kinase（p38 MAPK） . Methods The expression of integrin beta 3 and TN-c in 80 cases of breast cancer was studied by using immunohistochemistry. The expression of p-p38 and MMP-2 was determined by western blot while integrin beta3 and p38MAPK were blocked in MDA-MB-231 breast cancer cell line. Results Integrinβ3 and TN-c were overexpressed in breast cancer with correlation between integrinβ3 and TN-c,and the overexpression was correlated to lymph node metastasis and TNM stage in breast cancer. The expression level of p-p38 and MMP-2 decreased after integrinβ3 was blocked by integrinβ3 antibody,and the expression level of MMP-2 decreased after SB203580 was added in the MDA-MB-231 cell line. Conclusion Integrinβ3 and TN-c were overexpressed in breast cancer with the positive correlation between them,inhibition of integrin β3 expression could decrease the expression of MMP-2 through p38 MAPK in breast cancer.

关 键 词：人乳腺癌 P-P38 整合素 基质金属蛋白酶-2 

分 类 号：R737.9[医药卫生—肿瘤]