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Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma
Author(s) -
Zhang Zhe,
Sun Di,
Van Do Nguyen,
Tang Anzhou,
Hu Lifu,
Huang Guangwu
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22185
Subject(s) - methylation , nasopharyngeal carcinoma , cancer research , dna methylation , biology , bisulfite sequencing , cpg site , gene expression , gene , medicine , genetics , radiation therapy
RASSF2 can bind directly to K‐Ras and function as a negative effector of Ras protein. RASSF2A is the only isoform of RASSF 2 that contains CpG islands in its promoter and it has been reported to be inactivated by its promoter methylation in several human cancers. In the present study, we investigated the correlation of RASSF 2A expression with its promoter methylation in nasopharyngeal carcinoma (NPC). Expression of RASSF 2A was down‐regulated in 80% (4/5) of NPC cell lines. Decreased RASSF 2A expression was also observed in NPC primary tumors compared with normal nasopharyngeal epithelia. Promoter methylation of RASSF 2A could be detected in all the RASSF 2A ‐silenced cell lines (4/5) of the NPC cell lines and 50.9% (27/53) of primary tumors, but not in any of the normal epithelia. RASSF 2A ‐methylated cases showed a significantly lower level of RASSF 2A expression than unmethylated cases. Loss of RASSF 2A expression can be greatly restored by the methyltransferase inhibitor 5‐aza‐dC in NPC cell lines. In addition, patients with methylated RASSF 2A presented a higher frequency of lymph node metastasis ( p < 0.05). Ectopic expression of RASSF 2A in RASSF 2A ‐silenced and ‐methylated NPC cell line CNE2 shows that RASSF 2A could inhibit cell cycle progression, colony formation and cell migration, which provided further evidence that RASSF 2A is a candidate tumor suppressor gene. In conclusion, RASSF 2A , a candidate tumor suppressor gene (TSG), is frequently inactivated by its promoter methylation and this aberrant methylation correlates with lymph node metastasis in NPC. © 2006 Wiley‐Liss, Inc.