MMP-26在子宫内膜癌组织中的表达

Expression of MMP-26 in Tissues of Endometrial Carcinoma

【目的】研究MMP-26和ER-α在正常子宫内膜、子宫内膜非典型增生和子宫内膜癌组织中的表达及其与临床病理特征之间的关系。【方法】采用免疫组化和RT-PCR方法检测41例子宫内膜癌组织,12例子宫内膜非典型增生组织和10例正常子宫内膜组织中MMP-26和ER-α的蛋白表达及MMP-26mRNA表达水平并结合临床病理特征进行分析。统计采用秩和检验方法。【结果】MMP-26蛋白主要定位于子宫内膜腺上皮细胞、小血管壁和肿瘤细胞中。免疫组化及RT-PCR半定量分析表明:MMP-26在癌组织中表达下调,并随着肿瘤分化程度的降低,MMP-26表达逐渐下降。腺癌高分化组MMP-26蛋白表达强于中分化组(u=2.133,P=0.033)和低分化组(u=2.899,P=0.004)。低分化组MMP-26mRNA含量明显少于中分化组(U=2.123,P=0.034)和高分化组(U=2.477,P=0.013)。由于MMP-26表达模式和ER-α相似,作者对MMP-26启动区域进行分析,发现-130～-116位点间的序列与公认的ERE高度同源。【结论】MMP-26与ER-α表达相仿,在癌组织中表达下调,MMP-26启动区含有潜在的ERE序列,ER-α可能参与了MMP-26基因的调节。

[Objective]To study the expression of Metalloproteinase-26 （MMP-26） and estrogen receptor-α（ER-α） in normal, premalignant and malignant endometrial samples, and their correlations with tumor clinical characters. [Methods]A total of 41 cases of endometrial carcinoma samples, 12 of premalignant samples and 10 of normal endometrial tissue were tested for expression of MMP-26 and ER-α by immunohistochemistry and RT-PCR. Rank test was used to evaluate the significance of differences between the groups. [Results] Immunostaining localized MMP-26 in epithelial glandular and luminal cells, in vessel walls, and in tumor cells. Semi-quantifications with immunohistochemistry and RT-PCR revealed that expression of MMP-26 was down regulated in malignant group, and the amount of MMP-26 decreased progressively with loss of histological differentiation. Semiquantitative evaluation of MMP-26 protein by immunohistochemistry indicated that the signal was stronger in well than in moderately（u= 2. 133, P = 0. 033）differentiated, and stronger in well than in poorly（u= 2. 899, P =0. 004） differentiated samples. Semiquantitative evaluation of MMP-26 mRNA by RTPCR showed that the level was lower in poorly differentiated than in moderately （u= 2. 123, P =0. 034） and well （u= 2. 477, P = 0. 013） differentiated samples. Since the pattern of MMP-26 expression mimicked that of ER-α, the promoter region was researched to find that a sequence at position-130 to -116 had high homology to the consensus sequence of an ERE. [Conclusion]MMP-26 protein is selectively localized in the epithelial compartment of normal, premalignant, and malignant endometrial tissue. The pattern of MMP-26 expression mimics that of ER-α, and there might be a potential ERE in the promoter region of the MMP-26 gene. Based on these observations, it is suggested that ER-α might be involved in the regulation of the MMP-26 gene.