Tissue factor pathway inhibitor-2 suppresses the production of active matrix metalloproteinase-2 and is down-regulated in cells harboring activated ras oncogenes
Tissue factor pathway inhibitor-2 suppresses the production of active matrix metalloproteinase-2 and is down-regulated in cells harboring activated ras oncogenes
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DOI：
10.1016/s0014-5793(00)01902-5
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发表时间：
2000-09-08
期刊：
影响因子：
3.5
通讯作者：
Noda, M
中科院分区：
文献类型：
--
作者：
Izumi, H;Takahashi, C;Noda, M
将人胎盘cDNA表达文库转染到v- k -ras转化的NIH3T3细胞系DT中，筛选诱导平转的基因。其中一个基因被发现编码kuniz型丝氨酸蛋白酶抑制剂组织因子通路抑制剂-2 (TFPI-2)，虽然TFPI-2 mRNA可以在正常的人成纤维细胞（MRC-5）中检测到，但在表达活化的H-ras癌基因的MRC-5细胞和人纤维肉瘤细胞系HT1080中，TFPI-2 mRNA被下调。HT1080细胞中TFPI-2基因的表达恢复导致体外基质侵袭活性受到抑制，同时细胞分泌的活性基质金属蛋白酶-2的相对量减少。当DT细胞在条件培养基和tfpi -2转染HT1080细胞制备的细胞外基质中培养时，观察到附着增加和扁平逆转。这些结果表明，在正常组织中，TFPI-2可能是维持细胞外基质完整性所必需的，并且由于癌基因激活而导致的其下调可能有助于肿瘤细胞的恶性表型。(C) 2000年欧洲生化学会联合会。Elsevier Science B.V.版权所有。
A human placenta cDNA expression library was screened for genes inducing flat reversion when transfected into a v-K-ras-transformed NIH3T3 cell line, DT. One such gene was found to encode a Kunitz-type serine protease inhibitor, tissue factor pathway inhibitor-2 (TFPI-2), While the TFPI-2 mRNA can be detected in normal human fibroblasts (MRC-5), it is down-regulated in MRC-5 cells expressing an activated H-ras oncogene and in the human fibrosarcoma cell line, HT1080. Restored expression of the TFPI-2 gene in HT1080 cells resulted in the suppression of matrix invasion activity in vitro with concomitant decrease in the relative amount of active matrix metalloproteinase-2 secreted from the cells. When DT cells were cultured in the presence of conditioned medium and extracellular matrix prepared from TFPI-2-transfected HT1080 cells, increased attachment and flat reversion were observed. These results suggest that TFPI-2 may be required for the maintenance of the integrity of extracellular matrix in normal tissues and its down-regulation as a result of oncogene activation may contribute to the malignant phenotypes of tumor cells. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.