1 Department of Neurosurgery, People's Hospital of Deyang City, Deyang 618000, China 
2 Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China 
3 Department of Neurobiology, the Third Military Medical University, Chongqing 400038, China

Abstract 

Objective 
To investigate the impact of all-trans retinoic acid (ATRA) on MDM2 gene expression in astrocytoma cell line SHG-44, and to provide basic data for further research on the progression mechanism and gene therapy of human astrocytoma. 
Methods 
The differential expressions of MDM2 gene and protein in SHG-44 cells were detected by cDNA microarray and Western blot, respectively, before and after treatment of ATRA. The expressions of MDM2 protein in WHO grade II and grade IV astrocytomas were determined by immunohistochemical streptavidin-peroxidase method. Some differentially expressed genes were selected randomly for Northern blot analysis. 
Results 
The intensity ratio of ATRA-treated to untreated SHG-44 cell was 0.37 in the cDNA microarray, suggesting that the expression of MDM2 gene was down-regulated in SHG-44 cells after treatment with ATRA. Some genes differentially expressed in the microarray were confirmed by Northern blot. Western blot demonstrated that the optical density ratios of MDM2 to β-actin in ATRA-treated and untreated SHG-44 were 14.02±0.35 and 21.40±0.58 (t = 24.728, P = 0.000), respectively, suggesting that the expression of MDM2 protein was inhibited in ATRA-treated SHG-44 cells. Moreover, the percentages of MDM2-positive protein were 24.00% (6/25) and 56.52% (13/23) (χ 2 = 5.298, P = 0.021) in WHO grade II and grade IV astrocytomas, respectively, suggesting that the expression of MDM2 protein may increase along with the elevation of astrocytoma malignancy. 
Conclusion 
ATRA can inhibit MDM2 gene expression in SHG-44 cells, and MDM2 is related to astrocytoma progression.

Keywords

all-trans retinoic acid; astrocytoma; SHG-44 cell line; MDM2; cDNA microarray

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