Korean J Pediatr.  2006 Apr;49(4):431-438. 10.3345/kjp.2006.49.4.431.

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

• Kim SY
• Kim SR
• Lee JC
• Yi HK
• Lee DY
• Hwang PH

• KMID: 2140910
• DOI: http://doi.org/10.3345/kjp.2006.49.4.431

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.

Keyword

p53; IGFBP-3; Glycosylation

MeSH Terms

Adenoviridae
Apoptosis
Blotting, Western
Breast Neoplasms
Genes, Tumor Suppressor
Genetic Therapy
Glycosylation*
Humans
Insulin-Like Growth Factor Binding Protein 3
Protein Processing, Post-Translational
Insulin-Like Growth Factor Binding Protein 3