Caveolin-1, a major structural component of caveolae, plays a key role in numbers of cell signaling processes. Down-regulation of Cav1 has been reported in several human cancers and was proposed as a potential prognostic marker. By comparing the SAGE profiles of nasopharyngeal carcinoma (NPC) cell line (c666-1) and normal NP outgrowth, we revealed complete loss of Cav1 expression in the cancer cells. To confirm the downregulation of Cav1 expression in NPC, we further measured Cav1 mRNA and protein expression in 3 NPC cell lines by real time PCR and Western Blotting. Loss of Cav1 expression were found in 1/3 (33.3%) NPC cell lines. We then studied the Cav1 expression in 139 cases primary tumors including both undifferentiated and well differentiated types by using immunohistochemical studies on paraffin tissue sections. We showed a complete down-regulation of Cav1 in the tumor cells in 133 of them (95.6%). This contrasted with the consistent positivity along the basement membrane of the covering normal epithelia. The findings demonstrated that loss of Cav1 expression is common in NPC and may play an important role in NPC tumrigenesis. To discover the mechanism of Cav1 silencing in nasopharyngeal carcinoma (NPC), we examined the methylation status in the CpG islands in 6 NPC cell lines and xenografts. The hypermethylation was found in 3 of 6 (50%) NPC cell lines and xenografts. Moreover, treatment with 5-aza-2’-deoxycytidine restored Cav1 expression in these NPC cells. The loss of Cav1 expression also correlated with Cav1 promoter methylation in 30 of 36 primary cases (83.3%). Neither mutation nor deletion was found in the NPC cell lines. Our results suggest that methylation silencing of Cav1 is a common and likely important mechanism of NPC tumorigenesis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]