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Expression and aberrant methylation of atrogin-1 gene in gastric cardia adenocarcinoma tissuse
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Abstract:
Objective : To investigate the expression and aberrant methylation of the atrogin-1 gene in gastric cardia adenocarcinoma (GCA). Methods: Tumor and normal tissue samples were collected from GCA patients (n=139) undergoing surgical treatment in the Fourth Hospital of Hebei Medical University between 2004 and 2008. DNA methylation in the atrogin-1 promoter was analyzed by bisulfite conversion-methylation specific polymerase chain reaction (BS-MSP), atrogin-1 mRNA abundance by RT-PCR, and density of immunoreactive signals for atrogin-1 and Smad4 by immunohistochemical staining. Results: The frequency of aberrant DNA methylation in the promoter region of atrogin-1 was significantly higher inGCA than in normal tissues (44.6% vs 3.6%, P<0.05). The methylation status of atrogin-1 in tumor tissues was associated with TNM stage and the degree of histological differentiation of the tumor (P<0.05). The mRNA and protein levels of atrogin-1 were significantly decreased in tumor tissues as compared with normal tissues (0.482 5±0.175 4 vs 0.896 9±0.290 1 and 34.5% vs 82.0%, respectively, P<0.01). there was a negative correlation between atrogin-1 methylation and atrogin-1 mRNA and protein levels (r=-0.256，P<0.01). Smad4 protein was detected in 46.0% of tumor tissues but in 95.7% of non-tumor tissue (P<0.01) and the protein level of smad4 was positively associated with that of atrogin-1 (r＝0604，P<0.01). Conclusion: Hypermethylation in the promoter region of the atrogin-1 gene and the resultant decrease in atrogin-1 protein synthesis may play an important role in the pathogenesis of gastric cardia adenocarcinoma.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81101854)
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