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Expression of Ras-association domain family 7 gene in esophageal squamous cell carcinoma: Association with disease development and DNA methylation
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Abstract:
Objective: To assess the expression of Ras-association domain family 7 (RASSF7) gene in esophageal squamous cell carcinoma (ESCC) in association with the disease pathogenesis and progression and to evaluate the effect of DNA methylation on RASSF7 expression. Methods: Sixty-nine patients diagnosed with ESCC in Hebei Medical University-Affiliated Fourth Hospital between 2011 and 2012 were recruited. Carcinoma and its surrounding non-carcinoma tissue specimens were collected from 69 of these patients. Four esophageal cancer cell lines (TE13, T.Tn, YES-2, and Ec109) were treated with DNA methyltransferase inhibitor 5-aza-2’-detoxycytidine (5-Aza-dC). RASSF7 mRNA abundance in the 69 tissue specimens and 4 esophageal cancer cell lines after 5-Aza-dC treatment were determined by RT-PCR and methylation specific polymerase chain reaction (MSP). RASSF7 protein content in the tissue specimens were assessed by immunohistochemical staining. Results：RASSF7 mRNA was detected in TE13, T.TN, Yes-2 cells but not in Ec109 cells. Treatment with 5-Aza-dC induced RASSF7 mRNA but significantly decreased RASSF7 mRNA levels in TE13, T.Tn, and Yes-2 cells. No aberrant RASSF7 methylation was detected in any of the four esophageal cancer cell lines studied, regardless of 5-aza-dC treatment. Carcinoma tissue specimens had significantly higher abundance of RASSF7 mRNA (0.63±008 vs 0.42±0.20, P<0.01) and a significantly higher rate of positive immunohistochemical staining for RASSF7 protein 56(81.2% vs 53.6%, P<0.01) as compared with the non-carcinoma normal tissue specimens, and both RASSF7 mRNA and protein were associated with lymph node metastasis and histological grade of ESCC. Methylation was detected neither in ESCC specimens nor in the corresponding non-carcinoma tissue specimens. Conclusion：The differential expression of RASSF7 in different esophageal cancer cell lines, ESCC tumor tissue and non-carcinoma tissues is not related to methylation status of RASSF7. Increased expression of RASSF7 in the ESCC tissue suggests a role for RASSF7 in the pathogenesis and metastasis of ESCC.
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Project Supported:
Project supported by the National Natural Science Foundation（No. 81101854）, and the Major Projects of Medical Research Foundation of Hebei Province（No. \[2012\]2056）
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