摘要目的 探讨乳腺癌中STAT3和基质金属蛋白酶(MMP)-2、MMP-9及其组织抑制剂TIMP-1的表达与上皮间质转化(EMT)的关系及其临床意义. 方法 应用反转录聚合酶链反应(RT-PCR)技术检测30例新鲜乳腺浸润性导管癌与对应癌旁正常乳腺组织STAT3基因mRNA的表达,并以免疫组织化学Envision二步法方法检测84例乳腺浸润性导管癌组织及对照组35例癌旁正常乳腺组织pSTAT3和MMP-2、MMP-9及TIMP-1蛋白的表达. 结果 乳腺癌组织中STAT3mRNA相对定量显著高于癌旁正常乳腺组织(t=4.513,P=0.000);pSTAT3、MMP-2、MMP 9及TIMP-1蛋白在乳腺癌组织中的阳性表达率明显高于对照组,二者比较差异有统计学意义(均P＜0.05),乳腺癌组织中pSTAT3表达与MMP-2、MMP-9及TIMP-1的表达呈正相关(均P＜0.05);pSTAT3、MMP-2在乳腺浸润性导管癌不同组织学分级、有或无淋巴结转移组间的阳性表达率均差异有统计学意义(P＜0.05);MMP-9阳性表达率在有、无乳腺癌淋巴结转移组间差异有统计学意义(P＜0.05),但在不同组织学分级组间表达差异无统计学意义(P＞0.05);TIMP-1的阳性表达率在不同乳腺癌组织学分级及有、无淋巴结转移组间均无统计学意义差异(P＞0.05).在不同年龄、肿瘤大小组间比较,上述蛋白的阳性表达率均无差异(P＞0.05). 结论 STAT3在乳腺癌中高表达与MMP-2、MMP-9及其抑制剂TIMP-1表达上调关系密切;活化的STAT3可能通过调节MMP-2、MMP-9的表达介导EMT过程,从而促进乳腺浸润性导管癌的侵袭转移.

abstractsObjective To investigate the relationship of STAT3 with expressions of MMP-2,MMP-9 and TIMP-1 and with epithelial-mesenchymal transition (EMT) in breast cancer cells,and to explore the clinical significances.Methods The mRNA of STAT3 and the protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 of breast cancer cells in 84 patients with breast cancer were determined by real-time RT-PCR technique and immunohistochemical method in paraffin-embedded specimensm respectively.Normal breast tissues adjacent to breast cancer were taken as controls.Results mRNA expression of STAT3 was significantly higher in breast cancer tissues than in controls (t=4.513,P＜ 0.001).Protein expressions of pSTAT3,MMP-2,MMP-9 and TIMP-1 were higher in breast cancer tissues than in controls (all P＜ 0.05).There were positive correlations between pSTAT3 expression and the expressions of MMP-2,MMP-9 and TIMP-1 in breast cancer tissues (all P＜0.05).The higher levels of pSTAT3 and MMP-2 were associated with poorer differentiation and more lymph node metastasis of breast cancer (both P＜0.05).The positive expression of MMP-9 was correlated with lymph node metastasis (P＜0.05),but not with histological grading (P＞0.05).The positive expression of TIMP-1 had no associations with histological grading and lymph node metastasis (both P＞0.05).There were no significant differences in the protein expressions level of pSTAT3,MMP-2,MMP-9 and TIMP-1 between different ages and different breast tumor sizes (all P＞0.05).Conclusions The increased expression of STAT3 in breast cancer cells is closely correlated with the increased expressions of MMP-2,MMP-9 and STAT3 inhibitor TIMP-1.The activation of STAT3 gene can mediate EMT by inducing the protein expressions of MMP-2,MMP-9,which promotes the invasion and metastasis of breast cancer.