STAT3基因与MMP-2、MMP-9在乳腺浸润性导管癌中的表达及其相互关系

The expression and relationship of STAT3 gene and MMP-2、MMP-9 in breast infiltrating ductal carcinoma

目的磷酸化信号传导与转录激活因子3蛋白与乳腺浸润性导管癌中上皮间质转化(EMT)关系密切,EMT需要降解细胞外基质(ECM),而基质金属蛋白酶(MMPs)是降解ECM和基底膜(BM)的主要执行者。本研究从EMT角度探讨磷酸化信号传导与转录激活因子3(STAT3)基因与MMP-2、MMP-9蛋白在乳腺浸润性导管癌中的表达及其意义。方法应用RT-PCR技术检测30例新鲜乳腺癌及癌旁组织标本的STAT3基因的表达,并以免疫组化方法检测70例乳腺浸润性导管癌组织中pSTAT3、MMP-2和MMP-9的表达,分析pSTAT3蛋白与MMP-2、MMP-9表达的关系及其与临床病理参数的关系。结果 STAT3mRNA在乳腺癌标本中相对浓度为0.526±0.312,癌旁组织为0.197±0.161,两组间有显著统计学差异(P<0.05);pSTAT3、MMP-2、MMP-9在乳腺浸润性导管癌中阳性表达率分别为62.9%、72.8%、67.1%,明显高于正常乳腺组织19.2%、26.9%、34.6%,具有显著统计学差异(P均<0.05)。MMP-2、MMP-9在不同年龄、肿瘤大小、ER、PR表达组之间比较,差异无统计学意义,而在不同组织学分级、有无淋巴结转移之间,MMP-2、MMP-9表达有显著差异(P均<0.05)。结论 STAT3基因及pSTAT3与MMP-2、MMP-9表达在乳腺癌中呈正相关,STAT3基因及pSTAT3和MMP-2、MMP-9的高表达与乳腺癌的组织学分级与淋巴结转移相关,STAT3基因可能通过调节MMP-2、MMP-9的表达介导EMT从而促进乳腺浸润性导管癌的侵袭转移。

Objective The phosphorylated protein expression of signal transducer and activator of transcription 3 was asso- ciated with Epithelial-Mesenchymal Transition（EMT） in breast infiltrating ductal carcinoma（IDC）,and matrix metallopro- teinases （MMPs） plays an important role in EMT. This study aimed to investigate the expression and correlation among gene signal transducer and activator of transcription 3 （STAT3） and MMP-2,MMP-9 in IDC. Methods The mRNA ex- pression of STAT3 gene was detected in 32 cases of IDC by fluorescent real-time RT-PCR and the protein expression of pSTAT3 and MMP-2, MMP-9 was detected by immunohistochemistry. Results The mRNA expressions of STAT3 gene was significant increased in IDC compared with adjacent normal tissues （t = 4.513,P = 0.000）. The expression rate of pSTAT3 and MMP-2, MMP-9 in IDC was significant higher than in adjacent normal tissues group （P 〈 0.05 ）, and the pro- tein of pSTAT3 and MMP-2,MMP-9 was prominently expressed within the higher histology grades,metastasis of lymph nodes（P 〈 0.05）. There was positive relation between pSTAT3 and MMP-2,MMP-9 in IDC （P 〈 0.05）. Conclusion The expressions of STAT3 gene was significant increased in IDC,and STAT3 gene may play an important role in IDC via regu- lation of the expression of MMP-2, MMP-9 and Epithelial- Mesenehymal Transition.