乳腺癌组织中转化生长因子β1的表达及其介导乳腺癌侵袭和转移的机制

Expression of TGF-β1 and the mechanism of invasiveness and metastasis induced by TGF-β1 in breast cancer

目的探讨转化生长因子β1（TGF-β1）蛋白和mRNA在乳腺癌组织中的表达，及其与明胶酶和明胶酶抑制物的关系。方法建立组织芯片平台，应用免疫组化SP法检测160例乳腺癌组织TGF—B1、基质金属蛋白酶（MMP）-2、MMP-9、组织金属蛋白酶抑制物（TIMP）-1和TIMP-2蛋白的表达；应用原位分子杂交方法检测乳腺癌组织中TGF-β1 mRNA的表达。结果160例乳腺癌TGF-β1、MMP-2、MMP-9、TIMP-1和TIMP-2蛋白表达的阳性率分别为73．7％、96．9％、95．0％、87．5％和89．4％，TGF-β1 mRNA表达的阳性率为56．2％。TGF-β1的蛋白表达与腋窝淋巴结转移、TNM分期和c—erbB-2表达有关（P〈0．05，P〈0．05和P〈0．01），TGF—β1的mRNA表达与腋窝淋巴结转移有关（P〈0．05）。TGF-β1蛋白表达阳性组中位总生存期（OS）为60个月，中位无复发生存期（RFS）为59个月；TGF—β1蛋白表达阴性组中位OS为61个月，中位RFS为61个月，两组生存率差异无统计学意义（P=0．090），无复发生存率有统计学意义（P=0．023）。TGF-β1的蛋白表达与MMP-2和MMP-9的表达均呈正相关（r=0．170，P〈0．05；r=0．221，P〈0．01）。结论TGF-β1的表达与乳腺癌侵袭和转移密切相关，TGF—β1的蛋白产物通过调控MMP-2和MMP-9促进乳腺癌的侵袭和转移。

Objective To investigate the expression of MMP-2, TIMP-2, TGF-β1 and TGF-βRI and the relationship among them in breast cancer. Methods The protein expression of MMP-2, TIMP-2, TGF-β1 and TGF-βRI was detected on tissue chips by S-P immunohistochemical staining in 160 cases of breast carcinoma. Results The positive rates of TGF-β1, TGF-β1 mRNA, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression were 73.7%, 56.2%, 96.9%, 95.0% , 87.5% and 89.4%, respectively. Axillary lymph node metastasis and TNM staging（ P 〈 0.01 and P 〈 0. 01, respectively） were positively correlated to the expression of TGF-β1. Relase-free survival of TGF-β1 positive group was lower than that of TGF-β1 negative group（ P =0. 023 ）. The expression of MMP-2 or MMP-9 was positively correlated to that of TGF-β1 （r =0. 170, P 〈0.05;r =0.221, P 〈0.01） and was negatively correlated to that of TGF-β1 mRNA（r = -0. 126, P 〉0.05;r = O. 019, P 〉 0. 05 ）. Conclusion The expression of TGF-β1 may be closely correlated with the invasion and metastasis of breast cancer. TGF-β1-induced invasiveness and metastasis of breast cancer cells are mediated by MMP-2 and MMP-9.