摘要
目的研究基质金属蛋白酶(MMP)-26、金属蛋白酶组织抑制剂(TIMP)-4和雌激素受体(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。方法采用免疫组织化学和反转录-聚合酶链反应(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、TIMP-4和ER-α的蛋白表达及MMP-26 mRNA和TIMP-4 mRNA表达水平并结合临床病理特征进行分析。结果MMP-26和TIMP-4蛋白主要定位于子宫内膜腺上皮细胞和肿瘤细胞中。RT-PCR及免疫组织化学半定量分析结果表明:与正常子宫内膜和子宫内膜非典型增生组织相比,MMP-26低表达于子宫内膜癌组织(P均<0.05),并只与肿瘤组织分化程度密切相关。其中,腺癌高分化组MMP-26蛋白染色强于中分化组和低分化组(P均<0.05);低分化组MMP-26 mRNA含量也明显少于中分化组和高分化组(P均<0.05)。TIMP-4和ER-α同样在癌组织中低表达,并随着肿瘤分化程度的降低,二者表达逐渐减弱。癌组织中,MMP-26 mRNA/TIMP-4 mRNA随着肿瘤分化程度的下降、肌层浸润程度的加深和淋巴结的转移而升高(P均<0.05)。由于MMP-26、TIMP-4表达模式和ER-α相似,我们对其启动区域进行分析,发现MMP-26启动区域从-130至-116位点及TIMP-4启动区域-930至-916位点间的两段序列与公认的雌激素反应元件(ERE)高度同源。结论MMP-26和TIMP-4蛋白选择性地表达于子宫内膜的上皮部分。MMP-26、TIMP-4与ER-α表达相仿,在子宫内膜癌中表达下调。MMP-26、TIMP-4启动区域含有潜在的ERE序列,ER-α可能参与了MMP-26和TIMP-4基因水平的调节。
Objective To determine the expression of matrix metalloproteinase （MMP）-26, tissue inhibitor of metalloproteinase （TIMP）-4 and 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,TIMP-4 and ER-α by irnmunohistochemistry and RT-PCR. Rank test was used to evaluate the significance of difference between the groups. Results Immunostaining localized MMP-26 and TIMP-4 mainly in epithelial glandular and luminal cells, and in tumor cells. Semi-quantifications with RT-PCR and immunohistochemistry revealed that compared to normal （u = 2. 344, P = 0. 019; u = 2.161, P = 0. 039） and premalignant tissues （ u = 3. 054, P = 0. 002; u = 2. 640, P = 0. 008）, endometrial tumor expressed less MMP-26,and MMP-26 expression was only related to tumor histological differentiation. MMP-26 staining 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-26mRNA by RT-PCR showed that the level was lower in poorly differentiated than that in moderatly （u = 2. 123, P = 0. 034） and well （u = 2. 477, P = 0. 013） differentiated samples. Similarly, exgression of TIMP-4 and ER-α were down regulated in malignant tissue and decreased progressively with loss of tumor histological differentiation. In contrast, the level of MMP-26 mRNA/ TIMP-4 mRNA altered with loss of tumor histological differentiation, myometrial invasion and lymphatic metastases. Since the pattern of MMP-26 and TIMP-4 expression mimicked that of ER-α, we searched the promoter region for a potential estrogen response dement （ERE） and identified a putative ERE in the promoter region of the MMP-26 gene at position - 130 to - 116 and the TIMP-4 gene at position - 930 to - 916. Conclusion MMP-26 and TIMP-4 protein are selectively localized in the epithelial comparmaent of normal, prernalignant, and malignant endometrial tissue. The pattern of MMP-26 and TIMP-4 expression mimics that of ER-α, and there might be a potential ERE in the promoter region of the MMP-26 and TIMP-4 gene. Based on these observations, it is suggested that ER-α might be involved in the regulation of the MMP-26 and TIMP-4 gene.
出处
《山西医药杂志》
CAS
2007年第2期121-125,共5页
Shanxi Medical Journal
