Protocadherin 17 is a tumor suppressor and is frequently methylated in nasopharyngeal carcinoma.

PURPOSE

Several genes were shown to be downregulated or silenced in carcinomas and act as candidate tumor suppressor genes. However, the functions of in nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the promoter methylation status and its impact on the expression and functions of in NPC.

PATIENTS AND METHODS

To determine the mRNA levels and promoter methylation status of in NPC cell lines as well as 42 NPC patient specimens, we performed reverse transcription PCR, methylation-specific PCR, and bisulfite genome sequencing. The effects of ectopic expression in NPC cell lines were determined by colony formation, cell proliferation, wound healing, in vitro human umbilical vein endothelial cells tube formation, migration, invasion, cell cycle, and apoptosis assays and an in vivo subcutaneous tumor model.

RESULTS

expression was almost absent or significantly reduced in 100% of the NPC cell lines (5/5). However, 5-aza-2'-deoxycytidine and trichostatin A treatment restored expression. Promoter methylation was involved in silencing. Ectopic expression of in silenced NPC cells reduced colony formation, cell migration, angiogenesis, VEGF secretion, and tumorigenicity.

CONCLUSION

plays a tumor suppressor role in NPC. methylation may be a tumor-specific event and can be used as an epigenetic biomarker for NPC.