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The anti-tumor mechanisms of p53 through the regulation of expression and glycosylation of insulin-like growth factor binding protein-3  

Kim, Sun Young (Research Institute of Clinical Medicine, Chonbuk National University)
Kim, Se Rim (Research Institute of Clinical Medicine, Chonbuk National University)
Lee, Jung Chang (Department of Biochemistry, School of Dentistry, Chonbuk National University)
Yi, Ho Keun (Department of Biochemistry, School of Dentistry, Chonbuk National University)
Lee, Dae Yeol (Department of Pediatrics, School of Medicine, Chonbuk National University)
Hwang, Pyoung Han (Department of Pediatrics, School of Medicine, Chonbuk National University)
Publication Information
Clinical and Experimental Pediatrics / v.49, no.4, 2006 , pp. 431-438 More about this Journal
Abstract
Purpose : Insulin-like growth factor binding protein(IGFBP)-3 has been known as a tumor suppressor gene, and its anti-tumor function was divided into insulin-like growth factor(IGF)-dependent and IGF-independent mechanism. In IGF-independent mechanism, IGFBP-3 directly interacts with a cell without binding of IGFs, becoming an interesting object in oncology. Several studies demonstrate that one of the well-known tumor suppressor genes, p53, induces directly IGFBP-3 transcription, and the increment of IGFBP-3 expression induces apoptosis of many cancer cells. Recently, the anti-tumor mechanisms of IGFBP-3 have been reported, but post-translational modification of IGFBP-3 and its anti-tumor mechanism are not well known. In this study, we examined whether p53 regulated the glycosylation of IGFBP-3, and analysed the meaning of IGFBP-3 glycosylation related to the apoptosis of cancer cell. Methods : The p53-mutated status of MDA-MB-231 human breast cancer cells was used in this experiment. The expression and glycosylation of IGFBP-3 were tested by Western blot analysis after infection of adenovirus mediated Ad/p53 and/or Ad/IGFBP-3. Results : Ad/p53 infected cells resulted in growth retardation and the induced apoptosis. p53 induced direct expression and glycosylation of IGFBP-3. The increase of glcosylated IGFBP-3 was able to promote cellular apoptosis, and the glycosylation of IGFBP-3 was more activated by the double treatment of Ad/p53 and Ad/IGFBP-3. Conclusion : From this study, the anti-tumor activity of IGFBP-3 was shown to improve the stabilization of IGFBP-3 through the increment of glycosylation of IGFBP-3 by p53. This result suggests that the combined gene therapy of p53 and IGFBP-3 may appropriate treatment of cancer.
Keywords
p53; IGFBP-3; Glycosylation;
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