title: [Inactivation of PMS2 gene by promoter methylation in nasopharyngeal carcinoma].
abstract: Objective:To investigate the inactivation of PMS2 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 PMS2. The expressions of PMS2 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 PMS2, and the association of mRNA and protein expression of PMS2 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 PMS2 promoter methylation.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: H F
authors.initials: HF
authors.lastname: Ni
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: B
authors.initials: B
authors.lastname: Jiang
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Yuan
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Hangzhou First People's Hospital, Hangzhou 310006, China.
authors.forename: X L
authors.initials: XL
authors.lastname: Cao
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, China.
authors.forename: G W
authors.initials: GW
authors.lastname: Huang
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000494:pharmacology; D000077209:Decitabine; D015536:Down-Regulation; D004847:Epithelial Cells; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D000070976:Mismatch Repair Endonuclease PMS2 / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000077209:Decitabine; D015254:DNA Modification Methylases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D001374:Azacitidine