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Thrombomodulin‐mediated growth suppression is associated with G2/M phase arrest and requires p21CIP1/WAF1 expression
Author(s) -
Wu HuaLin,
Chang PoChiao,
Chen ChiaChi,
Chen PinShern,
Huang HueyChun,
Shi GueyYueh
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a38
Subject(s) - cell cycle , transfection , cyclin dependent kinase , cell growth , microbiology and biotechnology , cyclin a , cyclin dependent kinase 1 , cell cycle checkpoint , thrombomodulin , cyclin b1 , chemistry , flow cytometry , biology , cell , immunology , biochemistry , gene , thrombin , platelet
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 Ca 2+ ‐dependent interaction of lectin‐like domain. Recent studies have suggested that proteins with cell‐cell interaction 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 cycle flow cytometry also demonstrated that TMG‐transfected A2058 cells was arrested in G 2 /M phase. In addition, the expression levels of cdk1, cdk2, cyclin A, and cyclin B were decreased in TMG‐expressed cells. Furthermore, the expression levels of cdk inhibitor proteins, such as p21 CIP1/WAF1 , p27, and p19, were increased. Based on these results, we suggest that TM‐mediated growth arrest was dependent on p21 CIP1/WAF1 and cdk‐cyclin pathway. This finding indicates that TM may play an important role in cell proliferation and cell cycle progression.