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Archive > Volume 22 Issue 4 > 2015,22(4):472-478. DOI:10.3872/j.issn.1007-385X.2015.04.011 Prev Next
Clinical Research
Expression and methylation of IGFBP3 gene in esophageal squamous cell cancer
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Abstract:
Objective:To investigate the expression and methylation of IGFBP3 gene in esophageal squamous cell carcinoma (ESCC) cell lines and primary tumor tissues, and to explore the relationship between IGFBP3 expression and the clinical pathological features of ESCC. Methods: The mRNA and methylation status of IGFBP3 gene were detected by reverse transcription-PCR (RT-PCR) and methylation specific-PCR (MSP) using RNA and DNA from ESCC cell lines (TE1, TE13, YES-2,T.TN, Eca109) as well as primary tumor tissues and paired normal tissues from 82 ESCC patients. Immunohistochemistry was used to detect the expression of IGFBP3 in ESCC tissues. The relationship among aberrant methylation, expression of IGFBP3 gene, and clinical pathological features were analyzed with the SPSS 13.0 software. Results： IGFBP3 mRNA was undetectable or at very low level in ESCC cell lines examined (TE1, TE13, YES-2,T.TN, Eca109). However, its level increased significantly after the cells were treated with DNA methyltransferase inhibitor, 5-aza-2’-deoxycytidine (5-Aza-dC), indicating that IGFBP3 gene existed is hypermethylated in these cells (P<0.05). In primary tumor tissues from ESCC patients, IGFBP3 mRNA level (0.15±0.07) was significantly lower than that in corresponding normal tissues (0.88±0.32) (P＜0.01). Similarly, the positive rate of IGFBP3 (29.3%, 24/82) in ESCC tissues was significantly lower than that in corresponding normal tissues (84.1%, 69/82) (P<0.01). Thus, The methylation status of IGFBP3 gene associates with its mRNA and protein expression (P<0.05). Moreover, the methylation frequency of IGFBP3 gene in ESCC tissues (68.3%, 56/82) was increased significantly compared to that in corresponding normal tissues (15.9%, 13/82) (P<0.01) and associated with TNM stage of the tumors (P<0.05). The methylation frequency of IGFBP3 gene in stage Ⅲ-Ⅳ tumor tissues was significantly higher than that in stageⅠ-Ⅱtumor tissues (P<0.05). However, the methylation status of IGFBP3 in ESCC tissues was not associated with its pathological grade (P>0.05). Conclusion: The hypermethylation of IGFBP3 gene is a frequent event in ESCC cell lines and primary tumor tissues. The reduced expression of IGFBP3 caused by promoter hypermethylation of the gene may play an important role in the development of ESCC.
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Project Supported:
Project supported by the Science and Technology Plan Projects of Hebei Province（No. 122777117）, the Natural Science Foundation of Hebei Province (No.H2013206315), and the Focal Point Project of Medical Research of Hebei Province（No.20130543）
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