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Signal Transduction Factors on the Modulation of Radiosusceptibility in K562 Cells  

Yang Kwang Mo (Korea Institute of Radiological & Medical Sciences)
Youn Seon-Min (Department of Radiation Oncology, Eulji University School of Medicine)
Jeong Soo-Jin (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Jang Ji-Yeon (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Jo Wol-Soom (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Do Chang-Ho (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Yoo Y대-Jin (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Shin Young-Cheol (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Lee Hyung Sik (Department of Radiation Oncology, Dong-A University Hospital, College of Medicine)
Hur Won Joo (Department of Radiation Oncology, Dong-A University Hospital, College of Medicine)
Lim Young-Jin (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Jeong Min-Ho (The Institute of Medical Science (BK21 program), Dong-A University Hospital, College of Medicine)
Publication Information
Radiation Oncology Journal / v.21, no.3, 2003 , pp. 227-237 More about this Journal
Abstract
Purpose: The human chronic myelogenous leukemia cell line, K562, expresses the chimeric bcr-abl oncoprotein, whose deregulated protein tyrosine kinase activity antagonizes via DNA damaging agents. Previous experiments have shown that nanomolar concentrations of herbimycin A (HWA) coupled with X-irradiation have a synergistic effect in inducing apoptosis in the Ph-positive K562 leukemia cell line, but genistein, a PTK inhibitor, is non selective for the radiation-induced apoptosils on $p210^{bcr/abl}$ protected K562 cells. In these experiments, the cytoplasmic signal transduction pathways, the Induction on a number of transcription factors and the differential gene expression in this model were investigated. Materials and Methids: K562 cells in the exponential growth phase were used in this study. The cells were irradiated with 0.5-12 Gy, using a 6 Mev Linac (Clinac 1800, Varian, USA). Immediately after irradiation, the cells were treated with $0.25/muM$ of HMA and $25/muM$ of genistein, and the expressions and the activities of abl kinase, MAPK family, NF- kB, c-fos, c-myc, and thymidine kinase1 (TK1) were examined. The differential gene expressions induced by PTK inhibitors were also investigated. Results: The modulating effects of herbimycin A and genistein on the radiosensitivity of K562 cells were not related to the bcr-abl kinase activity. The signaling responses through the MAPK family of proteins, were not involved either in association with the radiation-induced apoptosis, which is accelerated by HMA, the expression of c-myc was increased. The combined treatment of genistein, with irradiation, enhanced NF- kB activity and the TK1 expression and activity. Conclusion: The effects of HMA and genistein on the radiosensitivity on the K562 cells were not related to the bcr-abl kinase activity in this study, another signaling pathway, besides the WAPK family responses to radiation to K562 cells, was found. Further evaluation using this model will provide valuable information for the optional radiosensitization or radioprotection.
Keywords
만성 골수성 백혈병;K562 세포;방사선유도 apoptosis;신호전달;
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