Lichtinghagen Ralf, Musholt Petra B, Lein Michael, Römer Andreas, Rudolph Birgit, Kristiansen Glen, Hauptmann Steffen, Schnorr Dietmar, Loening Stefan A, Jung Klaus
Department of Clinical Chemistry, University Medical School, Hannover, Germany.
Eur Urol. 2002 Oct;42(4):398-406. doi: 10.1016/s0302-2838(02)00324-x.
The aim of this study was to assess the behavior of the matrix metalloproteinases (MMPs) 2 and 9 and the tissue inhibitor of metalloproteinases 1 (TIMP-1) in human prostate cancer.
mRNA and protein expression patterns of MMP-2, MMP-9, and TIMP-1 were studied in cancerous and noncancerous parts of 17 prostates removed by radical prostatectomy. Competitive RT-PCR, gelatin-substrate zymography, and ELISA techniques were used for quantification.
On the mRNA level, MMP-2 expression was decreased and MMP-9, TIMP-1, the ratios of MMP-2 and MMP-9 to TIMP-1 were unchanged in cancerous tissue compared to the normal counterparts. On the protein level, expression of MMP-9 was significantly higher and TIMP-1 expression was significantly lower, MMP-2 was unchanged and the ratios of MMP-2 and MMP-9 to TIMP-1 were increased in tumor tissue.
The higher concentration of MMP-9 as well as the increased ratios of MMP-2 and MMP-9 to TIMP-1 in malignant tissue prove the proteolytic dysbalance in prostate cancer, which does not seem to be associated with the stage and grade of the tumor. Comparison of mRNA and protein expression of MMP-2, MMP-9 and TIMP-1, respectively, did not show any significant relationships illustrating the necessity to study these components at both molecular levels.
本研究旨在评估基质金属蛋白酶(MMPs)2和9以及金属蛋白酶组织抑制剂1(TIMP - 1)在人类前列腺癌中的表现。
对17例因根治性前列腺切除术切除的前列腺组织的癌组织和非癌组织中MMP - 2、MMP - 9和TIMP - 1的mRNA和蛋白表达模式进行研究。采用竞争性逆转录聚合酶链反应(RT - PCR)、明胶底物酶谱分析和酶联免疫吸附测定(ELISA)技术进行定量分析。
在mRNA水平上,与正常组织相比,癌组织中MMP - 2表达降低,MMP - 9、TIMP - 1以及MMP - 2和MMP - 9与TIMP - 1的比值无变化。在蛋白水平上,肿瘤组织中MMP - 9表达显著升高,TIMP - 1表达显著降低,MMP - 2无变化,MMP - 2和MMP - 9与TIMP - 1的比值升高。
恶性组织中MMP - 9浓度较高以及MMP - 2和MMP - 9与TIMP - 1的比值升高证明了前列腺癌中蛋白水解失衡,这似乎与肿瘤分期和分级无关。分别比较MMP - 2、MMP - 9和TIMP - 1的mRNA和蛋白表达,未显示任何显著相关性,这表明有必要在两个分子水平上研究这些成分。