Inactivation of RASSF2A by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma

✍ Scribed by Zhe Zhang; Di Sun; Do Nguyen Van; Anzhou Tang; Lifu Hu; Guangwu Huang

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 421 KB
• Volume: 120
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22185

✦ Synopsis

Abstract

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.