Inactivation of PMS2 gene by promoter methylation in nasopharyngeal carcinoma
10.3760/cma.j.issn.0253-3766.2016.11.003
- VernacularTitle:鼻咽癌中PMS2基因表达失活的甲基化调控机制
- Author:
Haifeng NI
1
;
Bo JIANG
;
Zhen ZHOU
;
Yong LI
;
Xiaoyang YUAN
;
Xiaolin CAO
;
Guangwu HUANG
Author Information
1. 310006杭州市第一人民医院耳鼻咽喉头颈外科
- Keywords:
Nasopharyngeal neoplasms;
DNA methylation;
PMS2;
Gene expression;
Pathology,clinical
- From:
Chinese Journal of Oncology
2016;38(11):812-817
- CountryChina
- Language:Chinese
-
Abstract:
[Abstrca t] Objective To investigate the inactivation of PMS 2 gene mediated by promoter methylation and its regulatory mechanism in nasopharyngeal carcinoma (NPC).Methods Fifty-four NPC tissues, 16 normal nasopharyngeal epithelia ( NNE) , 5 NPC cell lines ( CNE1, CNE2, TWO3, HNE1 and HONE1) and 1 normal nasopharyngeal epithelial cell line (NP69) were collected.Methylation-specific PCR (MSP) was used to detect the PMS2 promoter methylation, semi-quantitative reverse transcription PCR ( qRT-PCR) was applied to determine its mRNA expression , and immunohistochemistry ( IHC) was used to detect the protein expression of PMS 2.The expressions of PMS 2 mRNA in CNE1 and CNE2 cells before and after treated with methyltransferase inhibitor 5-aza-2-deoxycytidine were analyzed by qRT-PCR.The impact of methylation and demethylation on the mRNA expression of PMS 2, and the association of mRNA and protein expression of PMS 2 with clinicopathological features of nasopharyngeal cancer were analyzed .Results Methylation of PMS2 gene was detected in all of the five NPC cell lines , but not in normal nasopharyngeal epithelial NP69 cells.The methylation rate of PMS2 gene in NPC tissues was 63%(34/54), significantly higher than that of the normal nasopharyngeal epithelia (0/16, P<0.001).The expression levels of PMS2 mRNA and protein were significantly down-regulated in the 54 NPC tissues when compared with those in the 16 NNE tissues (P<0.001), and were also significantly lower in the 34 methylated NPC tissues than those in the 20 unmethylated NPC tissues (P<0.001).After treatment with 5-aza-2-deoxycytidine, the expression of PMS2 mRNA was restored in the CNE1 and CNE2 cells.However, the expressions of PMS2 mRNA and protein were not significantly correlated with patients′age, gender, TNM stage, histopathologic type or lymph node metastasis (P>0.05 for all).Conclusions Promoter methylation -mediated inactivation of PMS2 gene participates in carcinogenesis and development of NPC .PMS2 may be a candidate tumor suppressor in the treatment for patients with inactivation of PMS 2 promoter methylation .
