| Summary: | 碩士 === 國立成功大學 === 生物化學研究所 === 94 === Abstract
Thrombomodulin (TM) is an integral membrane glycoprotein that has a major role in anticoagulation. It is also demonstrated that TM may possess functions distinct from its anticoagulant activity. In the previous study, we showed that TM may function as a cell-cell adhesion molecule through a Ca2+ -dependent interaction of lectin-like domain. Recent studies have suggested that cell-cell interaction proteins such as cadherin family members play important roles as growth regulators in multiple tumor types. In order to study the influence of TM on cell cycle progression, TM-negative melanoma A2058 cells were transfected with green fluorescent protein (GFP)-tagged TM (TMG). The results showed that the proliferation rate of TMG-transfected A2058 cells was slower than vector control. Cell viability assay and DNA fragmentation assay showed that different proliferation rates between A2058 control and TMG was not due to cell apoptosis. In addition, cell cycle flow cytometry analysis demonstrated that TMG-transfected A2058 cells was arrested in G2/M phase. The expression levels of G2/M phase regulated proteins, including cdk1 and cyclin B were increased in A2058 TMG cells, but cdk2 and cyclinA were not. Furthermore, the expression levels of cdk inhibitor proteins, such as p21CIP1/WAF1 and p27 were increased in A2058 TMG cells. Based on these results, we suggested that TM-mediated growth arrest was dependent on p21CIP1/WAF1 and cdk-cyclin pathway. These finding indicated that TM may play an important role in cell proliferation and cell cycle progression.
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