Tissue factor pathway inhibitor‐2 suppresses the production of active matrix metalloproteinase‐2 and is down‐regulated in cells harboring activated ras oncogenes

FEBS Letters

Izumi, Hideki¹  Noda, Makoto¹  Oh, Junseo¹  Takahashi, Chiaki¹ 

[1] Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

关键词: ras oncogene;    Transformation suppressor gene;    Tissue factor pathway inhibitor-2;    Matrix metalloproteinase-2;    Tumor invasion;   

DOI  :  10.1016/S0014-5793(00)01902-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown