Abstract 3071: Frequent silencing of protocadherin 17, a candidate tumour suppressor for esophageal squamous-cell carcinoma

Abstract

Abstract Protocadherins are a subfamily of the cadherin superfamily, but little is known about their functions. We identified a homozygous loss of protocadherin 17 (PCDH17) in the course of a program to screen a panel of esophageal squamous-cell carcinoma (ESCC) cell lines for genomic copy-number aberrations. PCDH17 mRNA was expressed in normal esophageal tissue but not in the majority of ESCC cell lines without a homozygous deletion of this gene, and restored in gene-silenced ESCC cells after treatment with 5-aza-2′-deoxycytidine. The DNA methylation status of the PCDH17 CpG-island correlated inversely with the PCDH17 expression, and a putative methylation-target region showed promoter activity. The methylation of the PCDH17 promoter was also associated with the silencing of gene expression in primary ESCC at least partly. Among primary ESCC cases, the silencing of PCDH17 protein expression was associated with a poorer differentiation status of ESCC cells, and possibly with prognosis in a subset of this tumour. Restoration of PCDH17 expression in ESCC cells reduced cell proliferation and migration/invasion. These results suggest that silencing of PCDH17 expression through hypermethylation of the promoter or other mechanisms leads to loss of its tumour-suppressive activity, which may be a factor in the carcinogenesis of at least some ESCCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3071.