| Summary: | 碩士 === 臺北醫學大學 === 細胞及分子生物研究所 === 94 === Abstract
The K562 cells are one of the Bcr-Abl expressing chronic myelogenous leukemia (CML) cell lines. CML is a clonal myelo-proliferative disorder of the stem cells, which have lost their differentiation activity. Activin A is a pleiotropic cytokine belonging to the transforming growth factor (TGF)- superfamily. Activin A is known to be a commitment factor for erythroid differentiation. In a previous study, we showed that the cell fate determining role of the p38 MAPK pathway may be used as a tool to understand the molecular mechanisms for the proliferation and differentiation of K562 cells. Previously, we have used the PCR-select cDNA subtraction analysis to screen for genes involved in the undifferentiated status of K562 cells. In this study, we found that CD69 was down regulated by Activin A, and its expression level was restored by using the combination of p38 MAPK inhibitor SB203580 with Activin A. The Activin A-inhibited CD69 expression was reduced in K562-derived cells stably overexpressing the p38 dominant negative mutants, p38αAF or p38βAF, which was associated with increased cell proliferation and decreased differentiation. We further demonstrated that Activin A inhibited CD69 expression by deactivating ERK1/2. The exposure of K562 cells to the Bcr-Abl tyrosine kinase inhibitor STI571 resulted in decreased expression of CD69 mRNA and protein. In addition, Bcr-Abl was found to up-regulate CD69 promoter activity in BaF3 cells. To investigate the role of CD69 for CML cell function, the CD69 expressing plasmids were constructed. The role of CD69 in cell proliferation and differentiation of K562 cell was examined in the near future.
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