کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2552476 | 1560730 | 2009 | 10 صفحه PDF | دانلود رایگان |
AimsNm23-H1 is a suppressor of metastasis that has been implicated in the regulation of proliferation and differentiation of hematopoietic cells, although specific mechanisms for Nm23-H1 have not been well-characterized. Our study is designed to further elucidate the role of Nm23-H1 in the human chronic myeloid leukemia K562 cell line.Main methodsIn this study we generated and selected two cell clone pools of human chronic myeloid leukemia K562 cells with up-regulated and down-regulated Nm23-H1 expression.Key findingsOur data show that knockdown of Nm23-H1 decreased proliferation and increased the percentage of cells arrested in the G0/G1 phase of the cell cycle. Correspondingly, K562 cells overexpressing Nm23-H1 were more proliferative. After treatment of these two cell types with phorbol 12-myristate 13-acetate (PMA) for 48 h, cells with reduced Nm23-H1 expression had a higher percentage of 8N ploidy and higher expression of CD41 than K562 cells overexpressing Nm23-H1. A functional proteomics analysis identified ten proteins, including ANP32A, Cdc42GAP, and the isoform 2 of SET, whose expression levels were significantly altered by down-regulation of Nm23-H1. In addition, cells with decreased levels of Nm23-H1 had significantly reduced expression of Cdc42 independent of treatment with PMA. The interaction of the endogenous Nm23-H1 and Cdc42 proteins has been further validated by reciprocal immunoprecipitations.SignificanceWe provide data that complement functional studies of Nm23-H1 in regulating hematopoietic cells, and address action mechanisms of Nm23-H1 that have not previously been reported.
Journal: Life Sciences - Volume 84, Issues 13–14, 27 March 2009, Pages 458–467