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基质金属蛋白酶-26在人子宫内膜中表达,但在子宫内膜癌中不表达。

Matrix metalloproteinase-26 is expressed in human endometrium but not in endometrial carcinoma.

作者信息

Isaka Keiichi, Nishi Hirotaka, Nakai Hiromi, Nakada Toshihide, Feng Li Yin, Ebihara Yoshiro, Takayama Masaomi

机构信息

Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo 160-0023, Japan.

出版信息

Cancer. 2003 Jan 1;97(1):79-89. doi: 10.1002/cncr.11030.

Abstract

BACKGROUND

The human matrix metalloproteinase (MMP)-26, also called matrilysin-2 or endometase, has been isolated as a matrilysin (MMP-7) homolog. Matrix metalloproteinase-26 was expressed in tissue samples from the placenta and endometrial tumors and its expression may be related to the development of endometrial carcinomas.

METHODS

Total RNAs were isolated from 5 endometrial carcinoma cell lines, 36 normal endometrial tissue samples, 4 hyperplasia tissue samples, and from 24 endometrial carcinoma tissue samples. Reverse transcription-polymerase chain reation (RT-PCR) was performed to detect MMP-26 mRNA expression. To identify MMP-26 mRNA localization and protein expression, we performed in situ RT-PCR and immunohistochemistry, respectively.

RESULTS

Reverse transcription-polymerase chain reaction analysis revealed that MMP-26 mRNA was expressed in 24 of 36 normal human endometrial tissue samples. However, MMP-26 mRNA expression was not detected in endometrial carcinoma cell lines nor in endometrial carcinoma tissue samples except for one case. Western blot analysis showed similar results. In situ RT-PCR analysis revealed that MMP-26 expression was localized in the epithelial glandular cells but faint expression was observed in the stromal cells. Subsequently, we separated endometrial tissues into epithelial glandular and stromal cells. Using RT-PCR, the purified epithelial glandular cells exhibited MMP-26 mRNA expression but the purified stromal cells did not. Immunohistochemical analyses revealed that MMP-26 protein expression is also limited to endometrial epithelial glandular cells but not to cancer cells. Therefore, MMP-26 expression is limited to normal epithelial glandular cells.

CONCLUSIONS

We found a significant difference in MMP-26 expression in normal and malignant endometrial tissue samples, although its function is still unknown. These data suggest that MMP-26 may be a candidate for a new tumor marker for endometrial carcinomas.

摘要

背景

人基质金属蛋白酶(MMP)-26,也称为基质溶素-2或子宫内膜酶,已作为基质溶素(MMP-7)同源物被分离出来。基质金属蛋白酶-26在胎盘和子宫内膜肿瘤的组织样本中表达,其表达可能与子宫内膜癌的发生发展有关。

方法

从5种子宫内膜癌细胞系、36份正常子宫内膜组织样本、4份增生组织样本以及24份子宫内膜癌组织样本中提取总RNA。进行逆转录-聚合酶链反应(RT-PCR)以检测MMP-26 mRNA的表达。为了确定MMP-26 mRNA的定位和蛋白质表达,我们分别进行了原位RT-PCR和免疫组织化学检测。

结果

逆转录-聚合酶链反应分析显示,36份正常人类子宫内膜组织样本中有24份表达MMP-26 mRNA。然而,除1例样本外,在子宫内膜癌细胞系和子宫内膜癌组织样本中均未检测到MMP-26 mRNA表达。蛋白质印迹分析显示了类似的结果。原位RT-PCR分析显示,MMP-26表达定位于上皮腺细胞,但在基质细胞中观察到微弱表达。随后,我们将子宫内膜组织分离为上皮腺细胞和基质细胞。使用RT-PCR,纯化的上皮腺细胞显示出MMP-26 mRNA表达,而纯化的基质细胞则没有。免疫组织化学分析显示,MMP-26蛋白表达也仅限于子宫内膜上皮腺细胞,而非癌细胞。因此,MMP-26表达仅限于正常上皮腺细胞。

结论

我们发现正常和恶性子宫内膜组织样本中MMP-26表达存在显著差异,尽管其功能尚不清楚。这些数据表明,MMP-26可能是子宫内膜癌新肿瘤标志物的候选物。

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