- 作者: Hang Chang Kou-Gi Shyu Shankung Lin Shiow-Chwen TSai Bao-Wei WAng Ya-Chen Liu Yu-Ling Sung Chun-Chung Lee
- 作者服務機構: Surgical Department, Shin Kong Wu Ho-Su Memorial Hospital, and Surgical Department, Taipei Medical University, and Central Laboratory, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: The type-I plasminogen activator inhibitor(PAI一1),theprimary inhibitor of both tissue-type and urokinase-typeplasminogen activators (t-PA, u-PA),is the primary regu-lator of plasminogen activation and possibly of extracel-lular proteolysis.In anchorage-dependent cells, the PAI-1 gene is regulated by cell adhesion.PAI一1 gene expres-sion is induced more evidently in cells that adhered tothe culture plate than in those that did not adhere.In thisstudy, we further demonstrate that the PAI一1 gene ex-pression associated with cell adhesion is elicited throughthe activation of MEK and p42/p44 mitogen-activatedprotein(MAP) kinase(MAPK; ERK) signal pathways.Wefound that the MEK inhibitors, PD98059 and U0126,inhibited the induction of PAI一1 gene and protein expres-sion during cell adhesion,PD98059 also inhibited theadhesion of cells to the culture plate, and cell adhesionelicited the kinase activities of MEK and ERK. In addition,we illustrate that two transcription response elements,the serum response element (SRE)and the hypoxiaresponse element(HRE),which exist in the PAI一1 pro-moter, might be correlated with PAI-1 gene expressionduring cell adhesion.We discovered that the bindingability of nucleoproteins to both SRE and HRE wasenhanced by cell adhesion and was dependent on MEK.Based on these results, we suggest that both MEK andERK are involved in the induction of PAI-1 gene expres-sion during cell adhesion.Furthermore, the subsequentdownstream molecules, Elk-1 and HIF-1,may also partic-ipate.
- 中文關鍵字: --
- 英文關鍵字: Adhesion. Elk-1. HIF-1. MEK. p42/p44 ERK. PAI-1