The anti-tumor mechanisms of p53 through the regulation of expression and glycosylation of insulin-like growth factor binding protein-3.
10.3345/kjp.2006.49.4.431
- Author:
Sun Young KIM
1
;
Se Rim KIM
;
Jung Chang LEE
;
Ho Keun YI
;
Dae Yeol LEE
;
Pyoung Han HWANG
Author Information
1. Department of Pediatrics, School of Medicine, Chonbuk National University, Jeononju, Korea. hwaph@chonbuk.ac.kr
- Publication Type:Original Article
- Keywords:
p53;
IGFBP-3;
Glycosylation
- MeSH:
Adenoviridae;
Apoptosis;
Blotting, Western;
Breast Neoplasms;
Genes, Tumor Suppressor;
Genetic Therapy;
Glycosylation*;
Humans;
Insulin-Like Growth Factor Binding Protein 3;
Protein Processing, Post-Translational
- From:Korean Journal of Pediatrics
2006;49(4):431-438
- CountryRepublic of Korea
- Language:Korean
-
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.
