Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer.

ABSTRACT

PURPOSE: Protocadherin 10 (PCDH10), a homophilic cell adhesion member of the protocadherin family, plays important roles in calcium-dependent cell-cell adhesion and signal transduction. PCDH10 expression is downregulated in a number of different malignances, predominantly through promoter methylation-driven silencing. This study was designed to investigate PCDH10 expression and promoter methylation status in non-small cell lung cancer (NSCLC), and biological effects of PCDH10 in lung cancer cells. METHODS: The mRNA levels and promoter methylation status of PCDH10 were examined by RT-PCR and methylation-specific PCR (MSP) in lung cancer cell lines as well as primary lung tissue samples, and the clinical correlation of PCDH10 promoter methylation in NSCLC was further analyzed. The effects of PCDH10 re-expression in lung cancer cell lines was determined by cell proliferation, colony formation, and wound healing assays. RESULTS: PCDH10 expression was downregulated or silenced in 4/8 lung cancer cell lines but could be restored by treatment with 5-aza-2'-deoxycytidine and trichostatin A. PCDH10 was also downregulated in NSCLC tissues compared to their corresponding adjacent tissues. Promoter methylation of PCDH10 was observed in 50% (20/40) of the NSCLC tissues but not in tumor-adjacent or normal tissues, and PCDH10 promoter methylation was statistically related to smoking. Ectopic expression of PCDH10 in silenced cells can reduce lung cancer cell proliferation and migration. CONCLUSION: PCDH10 is frequently downregulated by promoter methylation and may serve as a tumor suppressor gene (TSG) in NSCLC.